Image summary: This is a photograph. The image depicts a healthcare professional performing an ultrasound examination on a patient in a clinical setting. The professional is wearing protective gear and operating an ultrasound machine, while the patient lies on an examination table. The ultrasound monitor displays a real-time internal scan of the patient. This suggests a diagnostic medical procedure is being conducted to evaluate the patient's internal health.

Development and Inheritance

Development, Inheritance, and Homeostasis

Both the genetic material inherited from parents (heredity) and normal development in the uterus (environment) play important roles in determining the homeostasis of a developing embryo and fetus and the subsequent birth of a healthy child.

In this chapter we will study the sequence of events from the fertilization of a secondary oocyte by a sperm to the formation of an adult organism. In particular, we focus on the developmental sequence from fertilization through implantation, embryonic and fetal development, labor, and birth. We will also examine the principles of inheritance (the passage of hereditary traits from one generation to another).

29.1 Overview of Development

Objectives

• Describe the sequence of events involved in development.

• Describe the trimesters of prenatal development.

As you learned in Chapter 28, sexual reproduction is the process by which organisms produce offspring by making sex cells called gametes gametes = spouses). Male gametes are called sperm and female gametes are called secondary oocytes. The organs that produce gametes are called gonads; these are the testes in the male and the ovaries in the female. Once sperm have been deposited in the female genital tract and a secondary oocyte has been released from the ovary, fertilization can occur. This process initiates a cascade of developmental events that, when completed properly, produces a healthy newborn baby.

Pregnancy is a sequence of events that begins with fertilization, proceeds to implantation, embryonic development, and fetal development, and ideally ends with birth about 38 weeks later, or 40 weeks after the mother's last menstrual period.

Development biology is the study of the growth and development of an individual from fertilization to death. From fertilization through the eighth week of development, the embryonic period, the developing human is called an embryo (em-= into; -bryo = grow). Embryology embryology is the study of development from the fertilized egg through the eighth week. The fetal period begins at week nine and continues until birth. During this time, the developing human is called a fetus (FÊ-tus = offspring).

Prenatal development prenatal; pre-= before; natal = birth) is the time from fertilization to birth and includes both the embryonic and fetal periods. Prenatal development is divided into periods of three calendar months each, called trimesters.

1. During the first trimester, the most critical stage of development, all of the major organ-systems begin to form. Because of this extensive, widespread activity, it is also the period when the developing organism is most vulnerable to the effects of drugs, radiation, and microbes.

2. The second trimester is characterized by the nearly complete development of organ systems. By the end of this stage, the fetus assumes distinctively human features.

3. The third trimester represents a period of rapid fetal growth in which the weight of the fetus doubles. During the early stages of this period, most of the organ systems become fully functional.

1. What is pregnancy?

2. What are the major events of each trimester?

29.2 The First Two Weeks of the Embryonic Period

Objective

• Explain the major events that occur during the first and second weeks of development.

First Week of Development

The embryonic period extends from fertilization through the eighth week. The first week of development is characterized by several significant events including fertilization, cleavage of the zygote, blastocyst formation, and implantation.

Fertilization During fertilization (fer'-ti-li-ZÃ-shun; fertil = fruitful), the genetic material from a haploid sperm and a haploid secondary oocyte merges into a single diploid nucleus. Of the 200 million sperm introduced into the vagina, fewer than 2 million (1%) reach the cervix of the uterus and only about 200 reach the secondary oocyte. Fertilization normally occurs in the uterine tube within 12 to 24 hours after ovulation.

Sperm can remain viable for about 48 hours after deposition in the vagina, although a secondary oocyte is viable for only about 24 hours after ovulation. Thus, pregnancy is most likely to occur if intercourse takes place during a 3-day window—from 2 days before ovulation to 1 day after ovulation.

Sperm swim from the vagina into the cervical canal by the whiplike movements of their tails (flagella). The passage of sperm through the rest of the uterus and then into the uterine tube results mainly from contractions of the walls of these organs. Prostaglandins in semen are believed to stimulate uterine motility at the time of intercourse and to aid in the movement of sperm through the uterus and into the uterine tube. Sperm that reach the vicinity of the oocyte within minutes after ejaculation are not capable of fertilizing it until about 7 hours later. During this time in the female genital tract, mostly in the uterine tube, sperm undergo capacitation (ka-pas-i-TÃ-shun; capacit-= capable of), a series of functional changes that cause the sperm's tail to beat even more vigorously and prepare its plasma membrane to fuse with the oocyte's plasma membrane. During capacitation, sperm are acted on by secretions in the female genital tract that result in the removal of cholesterol, glycoproteins, and proteins from the plasma membrane around the head of the sperm. Only capacitated sperm are capable of being attracted by and responding to chemical factors produced by the surrounding cells of the ovulated oocyte.

For fertilization to occur, a sperm first must penetrate two layers: the corona radiata (ko-Ro-na = crown; ra-de-A-ta = to radiate), the granulosa cells that surround the secondary oocyte, and the zona pellucida (Zo-na = zone; pelucida = allowing passage of light), the clear glycoprotein layer between the corona radiata and the oocyte's plasma membrane During fertilization, genetic material from a sperm and a secondary oocyte merge to form a single diploid nucleus.

(Figure 29.1a). The acrosome acrosome, a helmetlike structure that covers the head of a sperm (see Figure 28.6), contains several enzymes. Acrosomal enzymes and strong tail movements by the sperm help it penetrate the cells of the corona radiata and come in contact with the zona pellucida. One of the glycoproteins in the zona pellucida, called Z.P.3, acts as a sperm receptor.

Its binding to specific membrane proteins in the sperm head triggers the acrosomal reaction, the release of the contents of the acrosome. The acrosomal enzymes digest a path through the zona pellucida as the lashing sperm tail pushes the sperm onward. Although many sperm bind to Z.P.3 molecules and undergo acrosomal reactions, only the first sperm to penetrate the entire zona pellucida and reach the oocyte's plasma membrane fuses with the oocyte.

The fusion of a sperm with a secondary oocyte sets in motion events that block polyspermy polyspermy, fertilization by more than one sperm. Within a few seconds, the cell membrane of the oocyte depolarizes, which acts as a fast block to polyspermy—the inability of a depolarized oocyte to fuse with another sperm. Depolarization also triggers the intracellular release of calcium ions, which stimulate exocytosis of secretory vesicles from the oocyte. The molecules released by exocytosis inactivate Z.P.3 and harden the entire zona pellucida, events called the slow block to polyspermy.

Once a sperm enters a secondary oocyte, the oocyte first must complete meiosis 2. It divides into a larger ovum (mature egg) and a smaller second polar body that fragments and disintegrates (see Figure 28.15). The nucleus in the head of the sperm develops into the male pronucleus, and the nucleus of the fertilized ovum develops into the female pronucleus (Figure 29.1c). After the male and female pronuclei form, they fuse, producing a single diploid nucleus, a process known as syngamy syngamy. Thus, the fusion of the haploid (n) pronuclei restores the diploid number (2n) of 46 chromosomes. The fertilized ovum now is called a zygote (zygon = yoke).

Dizygotic (fraternal) twins are produced from the independent release of two secondary oocytes and the subsequent fertilization of each by different sperm. They are the same age and in the uterus at the same time, but genetically they are as dissimilar as any other siblings. Dizygotic twins may or may not be the same sex.

Because monozygotic (identical) twins develop from a single fertilized ovum, they contain exactly the same genetic material and are always the same sex. Monozygotic twins arise from separation of the developing cells into two embryos, which in 99% of the cases occurs before 8 days have passed. Separations that occur later than 8 days are likely to produce conjoined twins, a situation in which the twins are joined together and share some body structures.

Cleavage of the Zygote After fertilization, rapid mitotic cell divisions of the zygote called cleavage cleavage take place (Figure 29.2). The first division of the zygote begins about 24 hours after fertilization and is completed about 6 hours later. Each succeeding division takes slightly less time. By the second day after fertilization, the second cleavage is

Figure 29.2 summary: This figure is a series of biological diagrams and a micrograph. The diagrams illustrate the sequential stages of early embryonic development, starting from the cleavage of a zygote into two cells, then four cells, progressing to the morula stage, and finally forming a blastocyst shown from both external and internal perspectives. The micrograph at the bottom provides a real-world visualization of an early-stage embryo. The figure demonstrates that the early embryo undergoes rapid cell division while remaining encased within the zona pellucida. It concludes that the development progresses from a simple cluster of cells to a more complex structure characterized by the differentiation of the embryoblast, trophoblast, and the formation of a blastocyst cavity.

Figure 29.1 summary: This figure consists of a series of anatomical diagrams and micrographs. The content illustrates the sequential process of fertilization, showing sperm cells navigating through the corona radiata and zona pellucida to reach the plasma membrane and eventually the cytoplasm of a secondary oocyte, as well as a high-magnification view of a sperm head in contact with the oocyte and a light micrograph showing the formation of pronuclei. It can be inferred that fertilization requires the sperm to penetrate multiple protective layers of the oocyte to deliver genetic material, culminating in the fusion of male and female pronuclei.

Figure 29.2 Cleavage and the Formation of the Morula and Blastocyst.

Cleavage refers to the early, rapid mitotic divisions of a zygote. completed and there are four cells (Figure 29.2b). By the end of the third day, there are 16 cells. The progressively smaller cells produced by cleavage are called blastomeres blastomeres; blasto-= germ or sprout; -meres = parts). Successive cleavages eventually produce a solid sphere of cells called the morula morula = mulberry). The morula is still surrounded by the zona pellucida and is about the same size as the original zygote (Figure 29.2c).

Blastocyst Formation By the end of the fourth day, the number of cells in the morula increases as it continues to move through the uterine tube toward the uterine cavity. When the morula enters the uterine cavity on day 4 or 5, a glycogen-rich secretion from the glands of the endometrium of the uterus passes into the uterine cavity and enters the morula through the zona pellucida. This fluid, called uterine milk, along with nutrients stored in the cytoplasm of the blastomeres of the morula, provides nourishment for the developing morula.

At the 32-cell stage, the fluid enters the morula, collects between the blastomeres, and reorganizes them around a large fluid-filled cavity called the blastocyst cavity blastocyst; blasto-= germ or sprout; cyst-= bag), also called the blastocoel blastocoele (Figure 29.2e). Once the blastocyst cavity is formed, the developing mass is called the blastocyst. Though it now has hundreds of cells, the blastocyst is still about the same size as the original zygote.

During the formation of the blastocyst two distinct cell populations arise: the embryoblast and trophoblast (Figure 29.2e). The embryoblast embryoblast, or inner cell mass, is located internally and eventually develops into the embryo. The trophoblast trophoblast; tropho-= develop or nourish) is the outer superficial layer of cells that forms the spherelike wall of the blastocyst. It will ultimately develop into the outer chorionic sac that surrounds the fetus and the fetal portion of the placenta, the site of exchange of nutrients and wastes between the mother and fetus.

Around the fifth day after fertilization, the blastocyst "hatches" from the zona pellucida by digesting a hole in it with an enzyme, and then squeezing through the hole. This shedding of the zona pellucida is necessary in order to permit the next step, implantation (attachment) into the vascular, glandular endometrial lining of the uterus.

Implantation The blastocyst remains free within the uterine cavity for about 2 days before it attaches to the uterine wall. At this time the endometrium is in its secretory phase. About 6 days after fertilization, the blastocyst loosely attaches to the endometrium in a process called implantation (im-plant-Tâ-shun) (Figure 29.3). As the blastocyst implants, usually in either the posterior portion of the fundus or the body of the uterus, it orients with the inner cell mass toward the endometrium (Figure 29.3b). About 7 days after fertilization, the blastocyst attaches to the endometrium more firmly, endometrial glands in the vicinity enlarge, and the endometrium becomes more vascularized (forms new blood vessels). The blastocyst eventually secretes enzymes and burrows into the endometrium, and becomes surrounded by it.

Figure 29.3 summary: This figure consists of a series of anatomical diagrams. The content illustrates the positioning of a blastocyst within the uterine cavity, providing a broad view of the uterus, a close-up of the blastocyst contacting the endometrium, and a detailed cross-section of the implantation site. The diagrams identify key structures including the coronal plane, endometrial glands, blood vessels, the trophoblast, the embryoblast, and the blastocyst cavity. From these illustrations, it can be inferred that the blastocyst attaches to the lining of the uterus to begin the process of implantation, where the outer trophoblast layer interacts directly with the endometrial tissue to establish a connection with the maternal blood supply.

Following implantation, the functional layer of the endometrium is known as the decidua decidua = falling off).

Figure 29.3 Relationship of a Blastocyst to the Endometrium of the Uterus at the Time of Implantation.

Implantation, the attachment of a blastocyst to the endometrium, occurs about 6 days after fertilization.

Clinical Connection

Stem Cell Research and Therapeutic Cloning

A stem cell is a cell that is unspecialized (nonspecific in its functions) and has the ability to divide for indefinite periods and give rise to specialized (functionally specific) cells. Stem cells are classified into five principal types based on their ability to differentiate.

1. Totipotent totipotent; totus = whole; potentia = power) stem cells are cells that have the potential to form all of the nearly 220 different types of cells found in the human body. Examples of totipotent stem cells include a zygote (fertilized ovum) and cells (blastomeres) produced from the first several divisions of a zygote (a four-day-old embryo) that make up a blastocyst.

2. Pluripotent pluripotent; plur = several) stem cells or tissue-specific stem cells, are cells of an embryo past five days of

Q How does the blastocyst merge with and burrow into the endometrium? development and are derived from totipotent stem cells. They have the potential to form many (but not all) cells of the body. They cannot develop into extraembryonic structures such as the placenta, chorion, umbilical vesicle, and umbilical cord. Examples of pluripotent stem cells are the cells of the primary germ layers (endoderm, mesoderm, and ectoderm) and cells derived from them which go on to form the various tissues and organs of the body.

3. Multipotent multipotent; multi = many) stem cells are cells that can differentiate into a group of closely related cells. Examples are mesenchymal cells that can form almost all types of connective tissue and hemopoietic cells that can develop into myeloid stem cells and lymphoid stem cells.

4. Oligopotent oligopotent; oligo = few) stem cells are cells that develop into only a few cell types. Examples are myeloid

stem cells and lymphoid stem cells that differentiate into the different types of blood cells.

5. Unipotent unipotent; uni = one) stem cells are cells produce only one cell type. Examples are epidermal stem cells, which develop into epidermal cells only, and spermatogonia, which develop into sperm only.

One current application of stem cell research is bone marrow transplantation, in which donor bone marrow cells are used to replace cells destroyed by radiation, chemotherapy, or disease. This has been used to treat some blood-related diseases, such as leukemia. Studies have also suggested that stem cells in human adult red bone marrow have the ability to differentiate into cells of the liver, kidney, heart, lung, skeletal muscle, skin, and organs of the gastrointestinal tract. In theory, adult stem cells from red bone marrow could be harvested from a patient and then used to repair other tissues and organs in that patient's body without having to use stem cells from embryos. Stem cells have also been used to treat lymphomas, certain types of anemia, severe combined immunodeficiency disease S.C.I.D, multiple myeloma, and neuroblastoma. Stem cell therapy is being investigated to treat autoimmune diseases like diabetes and rheumatoid arthritis, inflammatory diseases, various types of cancer, brain injuries, stroke, Parkinson's disease, autism, dementia, cerebrovascular disease, liver disease, The decidua separates from the endometrium after the fetus is delivered, much as it does in normal menstruation. Different regions of the decidua are named based on their positions relative to the site of the implanted blastocyst (Figure 29.4). The basal decidua is the portion of the endometrium beneath the implanting embryo; it provides large amounts of glycogen and lipids for the developing embryo and fetus and later becomes the maternal part of the placenta. The capsular decidua is the

Figure 29.4 summary: This is an anatomical diagram. The figure presents a coronal section of the uterus alongside a detailed magnification of the decidua surrounding an implanted embryo. It identifies three distinct regions of the decidua: the capsular decidua which surrounds the embryo, the basal decidua located at the interface between the embryo and the uterine wall, and the parietal decidua which lines the remainder of the uterine cavity. The diagram illustrates that the decidua is specialized into different zones based on its proximity to the implanted embryo, with the basal region serving as the primary site for maternal placental development.

Figure 29.4 Regions of the Decidua.

The decidua is a modified portion of the endometrium that develops after implantation.

AIDS, osteoarthritis, and hearing loss, to name a few applications. Stem cell research could also be used to study how specific disease processes occur to help develop appropriate therapies. Finally, stem cells could provide a resource for testing new drugs for safety and effectiveness. portion of the endometrium that will cover the embryo after it implants in the endometrium the embryo and the uterine cavity. The parietal decidua (par-i-etal) is the remaining modified endometrium that lines the noninvolved areas of the rest of the uterus. As the embryo and later the fetus enlarge, and push into the uterine cavity, the capsular decidua becomes thin

Image summary: This is a scanning electron micrograph. The image displays several irregular, spiky cellular structures situated atop a textured, undulating surface of tissue. These protrusions appear as clusters of cells with numerous surface projections. The presence of these specialized cells on the tissue surface indicates an active biological interface, suggesting a process of cellular interaction or attachment between different tissue layers.

Clinical Connection

Ectopic Pregnancy

Ectopic pregnancy ectopic; ec = out of; -topic = place) is the development of an embryo or fetus outside the uterine cavity. An ectopic pregnancy usually occurs when movement of the fertilized ovum through the uterine tube is impaired by scarring due to a prior tubal infection, decreased movement of the uterine tube smooth muscle, or abnormal tubal anatomy. Although the most common site of ectopic pregnancy is the uterine tube, ectopic pregnancies may also occur in the ovary, abdominal cavity, or uterine cervix.

Women who smoke are twice as likely to have an ectopic pregnancy because nicotine in cigarette smoke paralyzes the cilia in the lining of the uterine tube (as it does those in the respiratory airways). Scars from pelvic inflammatory disease, previous uterine tube surgery, and previous ectopic pregnancy may also hinder movement of the fertilized ovum.

The signs and symptoms of ectopic pregnancy include one or two missed menstrual cycles followed by bleeding and acute abdominal and pelvic pain. Unless removed, the developing embryo can rupture the uterine tube, often resulting in death of the mother. Treatment options include surgery or the use of a cancer drug called methotrexate, which causes embryonic cells to stop dividing and eventually disappear. and eventually disappears as the enlarged fetus fills the uterine cavity and pushes against the surrounding perietal decidua. By about 27 weeks, the capsular decidua degenerates and disappears.

The major events associated with the first week of development are summarized in Figure 29.5.

Figure 29.5 summary: This figure is a biological diagram illustrating the sequence of early embryonic development. It depicts the female reproductive anatomy, including the ovary, uterine tube, and uterus, while tracing the journey of a developing embryo from fertilization to implantation. The diagram outlines a chronological progression starting with ovulation and fertilization in the uterine tube, followed by the cleavage stage, the formation of a morula, and the development into a blastocyst as it moves toward the uterine cavity, ultimately ending with implantation into the endometrium. The figure demonstrates that early development is a multi-step process occurring over several days, moving from the site of fertilization in the uterine tube to the final attachment within the uterine wall.

Second Week of Development

Development of the Trophoblast About 8 days after fertilization, the trophoblast develops into two layers in the region of contact between the blastocyst and endometrium. These are a syncytiotrophoblast syncytiotrophoblast that contains no distinct cell boundaries and a cytotrophoblast cytotrophoblast between the embryoblast and syncytiotrophoblast that is composed of distinct cells (Figure 29.6a). The two layers of trophoblast become part of the chorion (one of the fetal membranes) as they undergo further growth (see Figure 29.11a inset). During implantation, the syncytiotrophoblast secretes enzymes that enable the blastocyst to penetrate the uterine lining by digesting and liquefying the endometrial cells. Eventually, the blastocyst becomes buried in the endometrium and inner one-third of the myometrium.

Another secretion of the trophoblast is human chorionic gonadotropin (hCG), which has actions similar to luteinizing hormone (L.H). Human chorionic gonadotropin rescues the corpus luteum from degeneration and sustains its secretion of progesterone and estrogens. These hormones maintain the uterine lining in a secretory state, preventing menstruation. Peak secretion of hCG occurs about the ninth week of pregnancy, at which time the placenta is fully developed and produces the progesterone and estrogens that continue to sustain the pregnancy. The presence of hCG in maternal blood or urine is an indicator of pregnancy and is detected by home pregnancy tests.

Development of the Bilaminar Embryonic Disc

Like those of the trophoblast, cells of the embryoblast also differentiate into two layers around 8 days after fertilization: a hypoblast (primitive endoderm) and epiblast (primitive ectoderm) (Figure 29.6a). Cells of the hypoblast and epiblast together form a flat disc referred to as the bilaminar embryonic disc bilaminar = two-layered). Soon, a small cavity appears within the epiblast and eventually enlarges to form the amniotic cavity amniotic; amnio-= membrane).

Development of the Amnion As the amniotic cavity enlarges, a single layer of squamous cells forms a domelike roof above the epiblast cells called the amnion amnion amnio = membrane) (Figure 29.6a). Thus, the amnion forms the roof of the amniotic cavity, and the epiblast forms the floor. Initially, the amnion overlies only the bilaminar embryonic disc. However, as the embryonic disc increases in size and begins to fold, the amnion eventually surrounds the entire embryo (see Figure 29.11a inset), creating the amniotic cavity that becomes filled with amniotic fluid amniotic. Most amniotic fluid is initially derived from maternal blood.

Later, the fetus contributes to the fluid by excreting urine into the amniotic cavity. Amniotic fluid serves as a shock absorber for the fetus, helps regulate fetal body temperature, helps prevent the fetus from drying out, and prevents adhesions between the skin of the fetus and surrounding tissues. The amnion usually ruptures just before birth; it and its fluid constitute the “bag of waters.” Embryonic cells are normally sloughed off into amniotic fluid. They can be examined in a procedure called

Figure 29.6 Principal Events of the Second Week of Development.

amniocentesis, which involves withdrawing some of the amniotic fluid that bathes the developing fetus and analyzing the fetal cells and dissolved substances (see Section 29.6).

Development of the Umbilical Vesicle Also on the eighth day after fertilization, cells at the edge of the hypoblast About 8 days after fertilization, the trophoblast develops into a syncytiotrophoblast and a cytotrophoblast; the embryoblast develops into a hypoblast and epiblast (bilaminar embryonic disc).

Figure 29.6 Continued migrate and cover the inner surface of the blastocyst wall (Figure 29.6a). The migrating columnar cells become squamous (flat) and then form a thin membrane referred to as the extraembryonic endoblast (exocoelomic membrane). Together with the hypoblast, the exocoelomic membrane forms the wall of the umbilical vesicle (yolk sac), the former blastocyst cavity during earlier development (Figure 29.6b). As a result, the bilaminar embryonic disc is now positioned between the amniotic cavity and umbilical vesicle.

Figure 29.6 summary: This figure consists of a series of anatomical diagrams. The diagrams illustrate the progressive stages of a blastocyst embedding within the endometrium of the uterus following fertilization. Key structures identified across the stages include the bilaminar embryonic disc composed of the epiblast and hypoblast, the amniotic cavity, and the trophoblast layers consisting of the cytotrophoblast and syncytiotrophoblast. The sequence shows the development of the umbilical vesicle, the formation of extraembryonic endoblast, and the emergence of trophoblastic lacunae. As the process advances, the diagrams demonstrate the establishment of a lacunar vascular circle and the interaction between maternal sinusoids and the developing chorion, indicating the increasing complexity of the maternal-fetal interface for nutrient and gas exchange.

Since human embryos receive their nutrients from the endometrium, the umbilical vesicle is relatively empty and small, and decreases in size as development progresses (see Figure 29.11a). Nevertheless, the umbilical vesicle has several important functions in humans: supplies nutrients to the embryo during the second and third weeks of development; is the source of blood cells from the third through sixth weeks; contains the first cells (primordial germ cells) that will eventually migrate into the developing gonads, differentiate into the primitive germ cells, and form gametes; forms part of the digestive canal; functions as a shock absorber; and helps prevent drying out of the embryo.

Development of Sinusoids On the ninth day after fertilization, the blastocyst becomes completely embedded in the endometrium. As the syncytiotrophoblast expands, small spaces called trophoblastic lacunae lacunae = little lakes) develop within it (Figure 29.6b).

By the twelfth day of development, the trophoblastic lacunae fuse to form larger, interconnecting spaces called vascular circles (lacunar networks) (Figure 29.6c). Endometrial capillaries around the developing embryo become dilated and are referred to as maternal sinusoids (Si-nu-soyds). As the syncytiotrophoblast erodes some of the maternal sinusoids and endometrial glands, maternal blood and secretions from the glands enter the vascular circles and flow through them.

Maternal blood is both a rich source of materials for embryonic nutrition and a disposal site for the embryo's wastes.

Development of the Extraembryonic Coelom

About the twelfth day after fertilization, the extraembryonic mesoblast (extraembryonic mesoderm) mesoderm develops. These mesoblast cells are derived from the umbilical vesicle and form a connective tissue layer (mesenchyme) around the amnion and umbilical vesicle (Figure 29.6c). Soon a number of large cavities develop in the extraembryonic mesoblast, which then fuse to form a single, larger cavity called the extraembryonic coelom (SÉ-lom).

Development of the Chorion The extraembryonic mesoblast, together with the two layers of the trophoblast (the cytotrophoblast and syncytiotrophoblast), forms the chorion (KÖ-re-on = membrane) (Figure 29.6c). The chorion surrounds the embryo and, later, the fetus (see Figure 29.11a). Eventually it becomes the principal embryonic part of the placenta, the structure for exchange of materials between mother and fetus. The chorion also protects the embryo and fetus from the immune responses of the mother in two ways: (1) It secretes proteins that block antibody production by the mother; (2) it promotes the production of T lymphocytes that suppress the normal immune response in the uterus. Finally, the chorion produces human chorionic gonadotropin (hCG), an important hormone of pregnancy (see Figure 29.16).

Figure 29.16 summary: This figure consists of a flow chart and a corresponding line graph. The flow chart illustrates the hormones secreted by the placenta, including human chorionic gonadotropin, relaxin, human chorionic somatomammotropin, and corticotropin-releasing hormone, detailing their targets and physiological effects on the body during pregnancy and labor. The line graph tracks the blood levels of human chorionic gonadotropin, estrogens, and progesterone over the duration of the pregnancy from fertilization to birth. The data indicates that human chorionic gonadotropin levels peak early in pregnancy to maintain the corpus luteum before declining. In contrast, levels of estrogens and progesterone increase steadily throughout the pregnancy, reaching their highest concentrations near the time of birth.

The inner layer of the chorion eventually fuses with the amnion. With the development of the chorion, the extraembryonic coelom is now referred to as the chorionic cavity. By the end of the second week of development, the bilaminar embryonic disc becomes connected to the trophoblast by a band of extraembryonic mesoblast called the connecting (body) stalk (see Figure 29.7). The connecting stalk is the future umbilical cord.

Figure 29.7 summary: This figure is a series of anatomical diagrams. The illustrations depict the process of gastrulation, showing the progression from a bilaminar embryonic disc to a trilaminar embryonic disc. The sequence highlights the formation and organization of the epiblast and hypoblast, the appearance of the primitive streak and primitive node, and the eventual differentiation into the three primary germ layers: ectoderm, mesoderm, and endoderm. Based on the diagrams, it can be inferred that gastrulation involves a structural transformation where a two-layered disc reorganizes into a three-layered structure, establishing the primary body axes and the fundamental tissue layers necessary for further embryonic development.

3. Where does fertilization normally occur?

4. How is polyspermy prevented?

5. What is a morula, and how is it formed?

6. Describe the layers of a blastocyst and their eventual fates.

7. When, where, and how does implantation occur?

8. What are the functions of the trophoblast?

9. How is the bilaminar embryonic disc formed?

10. Describe the formation of the amnion, umbilical vesicle, and chorion, and explain their functions.

11. Why are sinusoids important during embryonic development?

29.3 The Remaining Weeks of the Embryonic Period

Objective

- Describe the major events that occur during the third through the eighth weeks of development.

Third Week of Development

The third embryonic week begins a 6-week period of very rapid development and differentiation. During the third week, the three primary germ layers are established and lay the groundwork for organ development in weeks 4 through 8.

Gastrulation The first major event of the third week of development, gastrulation (gas-troo-LÃ-shun), occurs about 15 days after fertilization. In this process, the bilaminar (twolayered) embryonic disc, consisting of epiblast and hypoblast, transforms into a trilaminar (three-layered) embryonic disc consisting of three layers: the ectoderm, mesoderm, and endoderm. These primary germ layers are the major embryonic tissues from which the various tissues and organs of the body develop.

Gastrulation involves the rearrangement and migration of cells from the epiblast. The first evidence of gastrulation is the formation of the primitive streak, a faint groove on the dorsal surface of the epiblast that elongates from the posterior to the anterior part of the embryo (Figure 29.7a). The primitive streak clearly establishes the head and tail ends of the embryo, as well as its right and left sides. At the head end of the primitive streak a small group of epiblastic cells forms a rounded structure called the primitive node.

Following formation of the primitive streak, cells of the epiblast move inward below the primitive streak and detach from the epiblast (Figure 29.7b) in a process called invagination (in-vaj'-i-Nã-shun). Once the cells have invaginated, some of them displace the hypoblast, forming the endoderm (endo-= inside; -derm = skin). Other cells remain between the epiblast and newly formed endoderm to form the mesoderm (meso-= middle). Cells remaining in the epiblast then form the ectoderm (ecto-= outside). The ectoderm and endoderm are epithelia composed of tightly packed cells; the mesoderm is a loosely organized connective tissue (mesenchyme).

As the embryo develops, the endoderm ultimately becomes the epithelial lining of the digestive canal, respiratory tract, and several other organs. The mesoderm gives rise to muscles, bones, and other connective tissues, and the peritoneum. The ectoderm develops into the epidermis of the skin and the nervous system. Table 29.1 provides more details about the fates of these primary germ layers.

Table 29.1 summary: This table categorizes various anatomical structures and tissues based on their origin from the three primary germ layers. The endoderm primarily gives rise to the epithelial linings of the digestive and respiratory systems, as well as associated glands. The mesoderm is responsible for the development of muscle, bone, circulatory and lymphatic systems, and the urogenital system. The ectoderm produces the nervous system, the epidermis of the skin, and the linings of several sensory organs and cranial cavities.

About 16 days after fertilization, mesodermal cells from the primitive node migrate toward the head end of the embryo and form a hollow tube of cells in the midline called the notochordal process notochordal (Figure 29.8). By days 22 to 24, the notochordal process becomes a solid cylinder of cells called

Figure 29.8 summary: This figure consists of two anatomical diagrams providing different perspectives of an early embryo. The first image shows a dorsal and partial sectional view, while the second image presents a sagittal section of the trilaminar embryonic disc during early development. The diagrams illustrate key embryonic structures, including the neural plate, primitive node, primitive streak, and the notochordal process. They also identify the oropharyngeal and cloacal membranes, the umbilical vesicle, the amniotic cavity, the mesoderm, the allantois, and the connecting stalk, while designating the head and tail ends of the embryo. Based on the anatomical arrangements, it can be inferred that the embryo has established a clear longitudinal axis and a trilaminar structure. The presence of the primitive streak and the developing notochordal process indicates that gastrulation is underway, facilitating the organization of the primary germ layers and the initiation of the central nervous system's foundation.

Clinical Connection

Anencephaly

Neural tube defects N.T.D's are caused by arrest of the normal development and closure of the neural tube. These include spina bifida (discussed in Disorders: Homeostatic Imbalances in Chapter 7) and anencephaly anencephaly; an-= without; -encephal = brain). In anencephaly, the cranial cavity bones fail to develop and

Figure 29.8 Development of the Notochordal Process.

certain parts of the brain remain in contact with amniotic fluid and degenerate. Usually, a part of the brain that controls vital functions such as breathing and regulation of the heart is also affected. Infants with anencephaly are stillborn or die within a few days after birth. The condition occurs about once in every 1000 births and is two to four times more common in female infants than males.

The notochordal process develops from the primitive node and later becomes the notochord. the notochord (Nô-tô-kord; noto-= back; -chord = cord). This structure plays an extremely important role in induction (indUK-shun), the process by which one tissue (inducing tissue) stimulates the development of an adjacent unspecified tissue (responding tissue) into a specialized one. An inducing tissue usually produces a chemical substance that influences the responding tissue. The notochord induces certain mesodermal cells to develop into the vertebral bodies. It also forms the nucleus pulposus of the intervertebral discs (see Figure 7.24).

Also during the third week of development, two faint depressions appear on the dorsal surface of the embryo where the ectoderm and endoderm make contact but lack mesoderm between them. The structure closer to the head end is called the oropharyngeal membrane oropharyngeal; oro-= mouth; pharyngeal = pertaining to the pharynx) (Figure 29.8a, b). It breaks down during the fourth week to connect the mouth cavity to the pharynx and the remainder of the digestive canal. The structure closer to the tail end is called the cloacal membrane (klo-A-kul = sewer), which degenerates in the seventh week to form the openings of the anus and urinary and reproductive tracts.

When the cloacal membrane appears, the wall of the umbilical vesicle forms a small vascularized outpouching called the allantois allantois; allant = sausage) that extends into the connecting stalk (Figure 29.8b). In nonmammalian organisms enclosed in an amnion, the allantois is used for gas exchange and waste removal. Because of the role of the human placenta in these activities, the allantois is not a prominent structure in humans (see Figure 29.11a). Nevertheless, it does function in the early formation of blood and blood vessels, and it is associated with the development of the urinary bladder.

Neurulation In addition to inducing mesodermal cells to develop into vertebral bodies, the notochord also induces ectodermal cells over it to form the neural plate (Figure 29.9a). (Also see Figure 14.27.) By the end of the third week, the lateral edges of the neural plate become more elevated and form the neural fold (Figure 29.9b). The depressed midregion is called the neural groove (Figure 29.9c). Generally, the neural folds approach each other and fuse, thus converting the neural plate into a neural tube (Figure 29.9d). This occurs first near the middle of the embryo and then progresses toward the head and tail ends. Neural tube cells then develop into the brain and spinal cord. The process by which the neural plate, neural folds, and neural tube form is called neurulation (noor-oo-LÃ-shun).

As the neural tube forms, some of the ectodermal cells from the tube migrate to form several layers of cells called the neural crest (see Figure 14.27b). Neural crest cells give rise to all sensory neurons and postganglionic neurons of the peripheral nerves, the suprarenal medullae, melanocytes (pigment cells) of the skin, arachnoid mater, and pia mater of the brain and spinal cord, and almost all of the skeletal and connective tissue components of the head.

At about 4 weeks after fertilization, the head end of the neural tube develops into three enlarged areas called primary brain vesicles (see Figure 14.28): the prosencephalon prosencephalon or forebrain, mesencephalon mesencephalon or midbrain, and rhombencephalon rhombencephalon or hindbrain. At about 5 weeks, the prosencephalon develops into secondary brain vesicles called the telencephalon telencephalon and diencephalon diencephalon, and the rhombencephalon develops into secondary brain vesicles called the metencephalon metencephalon and myelencephalon myelencephalon. The areas of the neural tube adjacent to the myelencephalon develop into the spinal cord. The parts of the brain that develop from the various brain vesicles are described in Section 14.1.

Development of Somites By about the 17th day after fertilization, the mesoderm adjacent to the notochord and neural tube forms paired longitudinal columns of paraxial mesoderm paraksial; para-= near) (Figure 29.9b). The mesoderm lateral to the paraxial mesoderm forms paired cylindrical masses called intermediate mesenchyme. The mesoderm lateral to the intermediate mesenchyme consists of a pair of flattened sheets called lateral plate mesoderm. The paraxial mesoderm soon segments into a series of paired, cubeshaped structures called somites (So-mits = little bodies).

By the end of the fifth week, 42 to 44 pairs of somites are present. The number of somites that develop over a given period can be correlated to the approximate age of the embryo.

Each somite differentiates into two distinct regions: a dermomytome, and a sclerotome (see Figure 10.17b). The dermomytome further differentiates into a dermatome that will contribute to the formation of the subcutaneous tissue and dermis, and a myotome, which will give rise to all the skeleton muscles of the trunk and limbs. The sclerotomes gives rise to the vertebrae and ribs.

Development of the Intraembryonic Coelom

In the third week of development, small spaces appear in the lateral plate mesoderm. These spaces soon merge to form a larger cavity called the intraembryonic coelom (Se-lom = cavity). This cavity splits the lateral plate mesoderm into two parts called splanchnopleuric mesenchyme and somatopleuric mesenchyme (Figure 29.9d). Splanchnopleuric mesenchyme splanknoplurik; splank = visceral; pleur = lung) forms the heart and the visceral layer of the serous pericardium, blood vessels, the smooth muscle and connective tissues of the respiratory and digestive organs, and the visceral layer of the serous membrane of the pleurae and peritoneum. Somatopleuric mesenchyme somatikplurik; soma-= body) gives rise to the bones, ligaments, blood vessels, and connective tissue of the limbs and the parietal layer of the serous membrane of the pericardium, pleurae, and peritoneum.

Development of the Cardiovascular System

At the beginning of the third week, angiogenesis anjeogenesis; angio-= vessel; -genesis = production), the formation of blood vessels, begins in the extraembryonic mesoblast in the umbilical vesicle, connecting stalk, and chorion. This early development is necessary because there is insufficient yolk in the umbilical vesicle and ovum to provide adequate nutrition for the rapidly developing embryo. Angiogenesis is initiated when mesodermal cells differentiate into hemangioblasts hemanjeoblasts. These then develop into cells called angioblasts,

Figure 29.9 Neurulation and the Development of Somites.

Neurulation is the process by which the neural plate, neural folds, and neural tube form. which aggregate to form isolated masses of cells referred to as blood islands (see Figure 21.32). Spaces soon develop in the blood islands and form the lumens of blood vessels. Some angioblasts arrange themselves around each space to form the endothelium and the tunics (layers) of the developing blood vessels. As the blood islands grow and fuse, they soon form an extensive system of blood vessels throughout the embryo.

About 3 weeks after fertilization, blood cells and blood plasma begin to develop outside the embryo from hemangioblasts in the blood vessels in the walls of the umbilical vesicle, allantois, and chorion. These then develop into multipotent stem cells that form blood cells. Blood formation begins within the embryo at about the fifth week in the liver and the twelfth week in the spleen, red bone marrow, and thymus.

The heart forms from splanchnopleuric mesenchyme in the head end of the embryo on days 18 and 19. This region of mesodermal cells is called the cardiogenic mesenchyme kardiogenik; cardio-= heart; -genic = producing). In response to induction signals from the underlying endoderm, these mesodermal cells form a pair of heart primordial tubes (see Figure 20.19). The tubes then fuse to form a single heart tube. By the end of the third week, the heart tube bends on itself, becomes S-shaped, and begins to beat. It then joins blood vessels in other parts of the embryo, connecting stalk, chorion, and umbilical vesicle to form a primitive cardiovascular system.

Figure 29.9 summary: This figure consists of a series of anatomical diagrams and transverse sections showing the progression of embryonic development. The illustrations depict the transformation of the embryo from an early stage to a more complex structure over several days, specifically highlighting the development of the neural system and mesodermal layers. The diagrams show the emergence of the neural plate, which subsequently folds to form the neural groove and eventually the neural tube. Simultaneously, the figure illustrates the development of the primitive streak, the formation of somites, and the differentiation of the mesoderm into paraxial, intermediate, and lateral plate mesoderm. The progression demonstrates the process of neurulation and the organization of the three primary germ layers, showing how the flat neural plate evolves into a tubular structure while surrounding tissues like the somites and the intraembryonic coelom develop in a coordinated manner.

Development of the Chorionic Villi and Pla-

centa As the embryonic tissue invades the uterine wall, maternal uterine vessels are eroded and maternal blood fills spaces, called trophoblastic lacunae (Figure 29.10) within the invading tissue. By the end of the second week of development, chorionic villi koreonik villi begin to develop. These fingerlike projections consist of chorion (syncytiotrophoblast surrounded by cytotrophoblast) that projects into the endometrial wall of the uterus (Figure 29.10a). By the end of the third week, blood capillaries develop in the chorionic villi (Figure 29.10b). Blood vessels in the chorionic villi connect to the embryonic heart by way of the umbilical arteries and umbilical vein through the connecting (body) stalk, which will eventually become the umbilical cord (Figure 29.10c). The embryonic blood capillaries within the chorionic villi project into the trophoblastic lacunae, which unite to form the intervillous spaces intervilus that bathe the chorionic villi with maternal blood. As a result, maternal blood bathes the chorion-covered fetal blood vessels.

Figure 29.10 summary: This figure consists of a series of anatomical diagrams. The images illustrate the structural development of the early embryo and its supporting membranes, highlighting the formation of the chorion, amniotic cavity, umbilical vesicle, and the connecting stalk. It details the interface between fetal and maternal tissues, specifically showing the arrangement of the syncytiotrophoblast, cytotrophoblast, and the development of chorionic villi within the intervillous space. The diagrams demonstrate the progression of placental development, showing how fetal blood capillaries within the villi establish a proximity to maternal sinusoids to facilitate exchange. It can be inferred that the complex folding and expansion of the chorionic villi significantly increase the surface area for nutrient and gas exchange between the maternal blood and the developing embryo.

Note, however, that maternal and embryonic blood vessels do not join, and the blood they carry does not normally mix. Instead, oxygen and nutrients in the blood of the mother's intervillous spaces, the spaces between chorionic villi, diffuse across the cell membranes into the capillaries of the villi. Waste products such as carbon dioxide diffuse in the opposite direction.

Placentation (plas-en-TÃ-shun) is the process of forming the placenta plasenta = flat cake), the site of exchange of nutrients and wastes between the mother and embryo/fetus. The placenta also produces hormones needed to sustain the pregnancy (see Figure 29.16). The placenta is unique because it develops from two separate individuals, the mother and the embryo.

By the beginning of the twelfth week, the placenta has two distinct parts: (1) the fetal portion formed by the chorionic villi of the chorion and (2) the maternal portion formed by the basal layer of the endometrium of the uterus (Figure 29.11a). When fully developed, the placenta is shaped like a pancake (Figure 29.11b). Functionally, the placenta allows oxygen and nutrients to diffuse from maternal blood into fetal blood while carbon dioxide and wastes diffuse from fetal blood into maternal blood. The placenta also is a protective barrier because

Figure 29.10 Development of Chorionic Villi.

Blood vessels in chorionic villi connect to the embryonic heart via the umbilical arteries and umbilical vein.

Q Why is development of chorionic villi important?

most microorganisms cannot pass through it. However, certain viruses, such as those that cause AIDS, German measles, chickenpox, measles encephalitis and other diseases, the placenta. Many drugs are used to cause birth problems.

Figure 29.11 Placenta and Umbilical Cord.

The placenta is formed by the chorionic villi of the embryo and the basal layer of the endometrium of the uterus of the mother. nutrients such as carbohydrates, proteins, calcium, and iron, which are released into fetal circulation as required.

The actual connection between the placenta and embryo, and later the fetus, is through the umbilical cord umbilikal = navel), which develops from the connecting stalk and is usually about 2 centimeters (1 in.) wide and about 50 to 60 centimeters (20 to 24 in.) in length. The umbilical cord consists of two umbilical arteries that carry deoxygenated fetal blood to the placenta, one umbilical vein that carries oxygen and nutrients acquired from the mother's intervillous spaces into the fetus, and supporting mucoid (mucous) connective tissue derived from the allantois. A layer of amnion surrounds the entire umbilical cord and gives it a shiny appearance (Figure 29.11). In some cases, the umbilical vein is used to transfuse blood into a fetus or to introduce drugs for various medical treatments.

Figure 29.11 summary: This figure consists of a series of anatomical diagrams and a biological illustration. The content depicts the structural organization of the placenta and umbilical cord, showing the embryo within the amniotic cavity surrounded by the amnion and chorion, a detailed cross-section of the maternal and fetal interface at the placenta, and a view of the fetal surface of the placenta. The diagrams illustrate the arrangement of the chorionic villi, the intervillous space containing maternal blood, and the network of umbilical arteries and veins. From these images, it can be inferred that the placenta serves as a complex exchange interface where maternal blood in the endometrial layer interacts with fetal blood within the chorionic villi without mixing. The umbilical cord acts as the vital conduit, utilizing arteries and veins to transport materials between the fetus and the placenta, while the amnion provides a protective covering for both the fetus and the fetal surface of the placenta.

In about 1 in 200 newborns, only one of the two umbilical arteries is present in the umbilical cord. It may be due to failure of the artery to develop or degeneration of the vessel early in development. Nearly 20% of infants with this condition develop cardiovascular defects.

After the birth of the baby, the placenta detaches from the uterus and is therefore termed the afterbirth. At this time, the umbilical cord is tied off and then severed. The small portion (about an inch) of the cord that remains attached to the infant begins to wither and falls off, usually within 12 to 15 days after birth.

The area where the cord was attached becomes covered by a thin layer of skin, and scar tissue forms. The scar is the umbilicus umbilikus or navel.

Clinical Connection

Placenta Previa

In some cases, the entire placenta or part of it may become implanted in the inferior portion of the uterus, near or covering the internal os of the cervix. This condition is called placenta previa prevea = before or in front of). Although placenta previa may lead to spontaneous abortion, it also occurs in approximately 1 in 250 live births.

It is dangerous to the fetus because it may cause premature birth and intrauterine hypoxia due to maternal bleeding. Maternal mortality is increased due to hemorrhage and infection. The most important symptom is sudden, painless, bright-red vaginal bleeding in the third trimester. Cesarean section is the preferred method of delivery in placenta previa.

Pharmaceutical companies use human placentas as a source of hormones, drugs, and blood; portions of placentas are also used for burn coverage. The placental and umbilical cord veins can also be used in blood vessel grafts, and cord blood can be frozen to provide a future source of pluripotent stem cells, for example, to repopulate red bone marrow following radiotherapy for cancer.

Fourth Week of Development

The fourth through eighth weeks of development are very significant in embryonic development because all major organs appear during this time. The term organogenesis organogenesis refers to the formation of body organs and systems. By the end of the eighth week, all of the major body systems have begun to develop, although their functions for the most part are minimal.

Organogenesis requires the presence of blood vessels to supply developing organs with oxygen and other nutrients. However, recent studies suggest that blood vessels play a significant role in organogenesis even before blood begins to flow within them. The endothelial cells of blood vessels apparently provide some type of developmental signal, either a secreted substance or a direct cell-to-cell interaction, that is necessary for organogenesis.

During the fourth week after fertilization, the embryo undergoes very dramatic changes in shape and size, nearly tripling its size. It is essentially converted from a flat, two-dimensional trilaminar embryonic disc to a three-dimensional cylinder, a process called embryonic folding (Figure 29.12a–d). The cylinder consists of endoderm in the center (gut), ectoderm on the outside (epidermis), and mesoderm in between. The main force responsible for embryonic folding is the different rates of growth of various parts of the embryo, especially the rapid longitudinal growth of the nervous system (neural tube). Folding in the median plane produces a head fold and a tail fold; folding in the horizontal plane results in the two lateral folds. Overall, due to the foldings, the embryo curves into a C-shape.

The head fold brings the developing heart and mouth into their eventual adult positions. The tail fold brings the developing anus into its eventual adult position. The lateral folds form as the lateral margins of the trilaminar embryonic disc bend ventrally.

As they move toward the midline, the lateral folds incorporate the dorsal part of the umbilical vesicle into the embryo as the primitive gut, the forerunner of the digestive canal (Figure 29.12b). The primitive gut differentiates into an anterior foregut, an intermediate midgut, and a posterior hindgut (Figure 29.12c). The fates of the foregut, midgut, and hindgut are described in Section 24.16. Recall that the oropharyngeal membrane is located in the head end of the embryo (see Figure 29.8). It separates the future pharyngeal (throat) region of the foregut from the stomodeum (sto-mo-De-um; stomo-= mouth), the future oral cavity. Because of head folding, the oropharyngeal membrane moves downward and the foregut and stomodeum move closer to their final positions. When the oropharyngeal membrane ruptures during the fourth week, the pharyngeal region of the pharynx is brought into contact with the stomodeum.

In a developing embryo, the last part of the hindgut expands into a cavity called the cloaca (klo-angstroms-ka) (see Figure 26.23). On the outside of the embryo is a small cavity in the tail region called the proctodeum (prok-tö-DÊ-um; procto-= anus) (Figure 29.12c). Separating the cloaca from the proctodeum is the cloacal membrane (see Figure 29.8). During embryonic development, the cloaca divides into a ventral urogenital sinus and a dorsal anorectal canal. As a result of tail folding, the cloacal membrane moves downward and the urogenital sinus, anorectal canal, and proctodeum move closer to their final positions. When the cloacal membrane ruptures during the seventh week of development, the urogenital and anal openings are created.

In addition to embryonic folding, development of somites, and development of the neural tube, four pairs of pharyngeal arches farinjeal or branchial arches brangkeal; branch = gill) begin to develop on each side of the future head and neck regions (Figure 29.13) during the fourth week. These four paired structures begin their development on the 22nd day after fertilization and form swellings on the surface of the embryo. Each pharyngeal arch consists of an outer covering of ectoderm and an inner covering of endoderm, with mesoderm in between. Within each pharyngeal arch there is an artery, a cranial nerve, cartilaginous skeletal rods that support the arch, and skeletal muscle tissue that attaches to and moves the cartilage rods.

Figure 29.13 summary: This figure consists of a series of anatomical diagrams providing an external view, a sagittal section, and a cross-section of an early embryo. The diagrams illustrate the development of the pharyngeal apparatus, labeling external features such as the pharyngeal arches, grooves, otic placode, lens placode, and somites. The internal views highlight the pharyngeal pouches, the thyroid diverticulum, the hypophyseal pouch, the stomodeum, and the developing brain and heart. The detailed cross-section identifies the internal components of the pharyngeal arches, including cartilages, nerves, muscles, and arteries, alongside the corresponding pharyngeal pouches and grooves. From these views, it can be inferred that the pharyngeal apparatus is a complex, multi-layered structure consisting of external arches and grooves that correspond to internal pouches and vascular elements. The spatial arrangement demonstrates that these structures develop in close proximity to other critical organs such as the brain and heart, forming the foundational architecture for various head and neck structures.

On the ectodermal surface of the pharyngeal region, each pharyngeal arch is separated by a groove called a pharyngeal groove (Figure 29.13a). The pharyngeal grooves meet corresponding balloonlike outgrowths of the endodermal pharyngeal lining called pharyngeal (branchial) pouches. Where the pharyngeal groove and pouch meet to separate the arches, the outer ectoderm of the cleft contacts the inner endoderm of the pouch and there is no mesoderm between (Figure 29.13b).

Just as the somite gives rise to specified structures in the body wall, each pharyngeal arch, groove, and pouch gives rise to specified structures in the head and neck. Each pharyngeal arch is a developmental unit and includes a skeletal component, muscle, nerve, and blood vessels. In the human embryo, there are four obvious pharyngeal arches.

Each of these arches develops into a specific and unique component of the head and neck region. For example, the first pharyngeal arch is often called the mandibular arch because it forms the jaws (the mandible is the lower jawbone).

The first sign of a developing ear is a thickened area of ectoderm, the otic placode plakod, or future internal ear, which can be distinguished about 22 days after fertilization. A thickened area of ectoderm called the lens placode, which will become the lens of the eye, also appears at this time (see Figure 29.13a).

By the middle of the fourth week, the upper limbs begin their development as outgrowths of mesoderm covered by ectoderm called upper limb buds (see Figure 8.16b). By the end of the fourth week, the lower limb buds develop. The heart also forms a distinct projection on the ventral surface of the embryo called the heart prominence (see Figure 8.16b). At the end of the fourth week the embryo has a distinctive tail (see Figure 8.16b).

Figure 29.12 Embryonic Folding.

Embryonic folding converts the two-dimensional trilaminar embryonic disc into a three-dimensional cylinder.

Figure 29.12 summary: This figure consists of a series of anatomical diagrams showing sagittal and cross-sectional views of an embryo. The illustrations depict the progressive developmental stages of the embryo over several days, highlighting the formation of key structures including the neural tube, notochord, and the primitive gut. The sequence shows the transition from a relatively flat embryonic disc to a folded three-dimensional structure, illustrating the emergence of the head and tail folds as well as lateral folds. These folding processes result in the internalization of the primitive gut, which is further differentiated into the foregut, midgut, and hindgut. The diagrams also track the development of the heart, the formation of the stomodeum and proctodeum, and the eventual closure of the abdominal wall, demonstrating the complex spatial reorganization required to establish the basic body plan and internal organ cavities.

Figure 29.13 Development of Pharyngeal Arches, Pharyngeal Grooves, and Pharyngeal Pouches.

The four pairs of pharyngeal pouches consist of ectoderm, mesoderm, and endoderm and contain blood vessels, cranial nerves, cartilage, and muscular tissue.

Fifth Through Eighth Weeks of Development

During the fifth week of development, there is a very rapid development of the brain, so growth of the head is considerable. By the end of the sixth week, the head grows even larger relative to the trunk, and the limbs show substantial development (see Figure 8.16c). In addition, the neck and trunk begin to straighten, and the heart is now four-chambered. By the seventh week, the various regions of the limbs become distinct and the beginnings of digits appear (see Figure 8.16d). At the start of the eighth week (the final week of the embryonic period), the digits of the hands are short and webbed, the tail is shorter. but still visible, the eyes are open, and the auricles of the ears are visible (see Figure 8.16c). By the end of the eighth week, all regions of limbs are apparent; the digits are distinct and no longer webbed due to removal of cells via apoptosis. Also, the eyelids come together and may fuse, the tail disappears, and the external genitals begin to differentiate. The embryo now has clearly human characteristics.

Checkpoint

12. When does gastrulation occur?

13. How do the three primary germ layers form? Why are they important?

14. What is meant by the term induction?

15. Describe how neurulation occurs. Why is it important?

16. What are the functions of somites?

17. How does the cardiovascular system develop?

18. How does the placenta form?

19. How does embryonic folding occur?

20. How does the primitive gut form, and what is its significance?

21. What is the origin of the structures of the head and neck?

22. What are limb buds?

23. What changes occur in the limbs during the second half of the embryonic period?

29.4

Fetal Period

Objective

• Describe the major events of the fetal period.

During the fetal period (from the ninth week until birth), tissues and organs that developed during the embryonic period grow and differentiate. Very few new structures appear during the fetal period, but the rate of body growth is remarkable, especially during the second half of intrauterine life. For example, during the last 2.5 months of intrauterine life, half of the full-term weight is added. At the beginning of the fetal period, the head is half the length of the body.

By the end of the fetal period, the head size is only one-quarter the length of the body. During the same period, the limbs also increase in size from one-eighth to one-half the fetal length. The fetus is also less vulnerable to the damaging effects of drugs, radiation, and microbes than it was as an embryo.

A summary of the major developmental events of the embryonic and fetal periods is illustrated in Figure 29.14 and presented in Table 29.2.

Figure 29.14 summary: This figure is a series of anatomical photographs and illustrations. The content shows the sequential stages of human prenatal development, starting from an early embryo and progressing to a fetus. Key anatomical landmarks are labeled at each stage, including the neural plate and primitive streak in the earliest phase, followed by the emergence of the heart prominence, brain, spinal cord, limb buds, and facial features such as the eyes, ears, and nose. As development progresses, the umbilical cord and limbs become more defined. The sequence demonstrates the rapid morphological transformation from a simple disc-like structure to a complex organism with recognizable human features, illustrating the progression of organogenesis and fetal growth over several weeks.

Table 29.2 summary: This table outlines the progression of prenatal growth and development across the embryonic and fetal periods. It shows a consistent increase in size and weight over time, alongside the sequential maturation of anatomical structures. Early development is characterized by the formation of primary germ layers, the heart, and basic body systems. As the fetus progresses, there is a shift toward refining human-like features, increasing proportionality between the head and body, and a significant accumulation of subcutaneous fat. The data highlights critical milestones in organ viability, such as the development of the lungs and central nervous system, which increase the likelihood of survival for premature births in later stages.

Throughout the text we have discussed the developmental anatomy of the various body systems in their respective chapters. The following list of these sections is presented here for your review.

• Integumentary System (Section 5.6)

• Skeletal System (Section 8.16)

• Muscular System (Section 10.11)

• Nervous System (Section 14.19)

• Endocrine System (Section 18.15)

• Heart (Section 20.8)

• Blood and Blood Vessels (Section 21.22)

• Lymphoid (lymphatic) System and Immunity (Section 22.5)

• Respiratory System (Section 23.10)

• Digestive System (Section 24.15)

• Urinary System (Section 26.10)

• Genital (Reproductive) Systems (Section 28.5)

Figure 29.14 Summary of representative developmental events of the embryonic and fetal periods. The embryos and fetuses are not shown at their actual sizes.

Development during the fetal period is mostly concerned with the growth and differentiation of tissues and organs formed during the embryonic period.

Clinical Connection

Fetal Surgery

Fetal (prenatal) surgery is a surgical procedure performed on a fetus with certain life-threatening congenital disorders in order to correct abnormalities that would be too far advanced to correct after birth. In most cases, fetal surgery is performed only when the fetus is not otherwise expected to survive delivery or live long enough for surgery after birth.

There are several techniques employed in fetal surgery. In open fetal surgery, an incision is made in the lower abdomen to expose the uterus. The uterus is then opened and the fetus is partially removed so that the area that requires surgery is exposed.

Table 29.2 Continues Once the corrective surgery is completed, the fetus is returned to the uterus and the uterus and abdomen are closed. In fetoscopic surgery, a small incision is made in the abdomen and an endoscope is inserted through the abdominal wall and uterus into the amniotic cavity. A fetal endoscope is an instrument that permits direct visualization of the fetus and consists of a flexible tube with a light, camera, and accessories for obtaining tissue samples and performing simple, minor surgeries.

Fetal surgery is performed to correct hydrocephalus, clear urinary tract and tracheal obstructions, repair heart and other organ defects, remove pulmonary cysts and tumors at the base of the backbone, and correct spina bifida, among other uses.

Chart 29.2 summary: This figure is a series of anatomical illustrations. It depicts the progressive growth and morphological changes of a human fetus at various stages of development, from the early embryonic phase through the late fetal period. The illustrations show a steady increase in overall body size, the refinement of facial features, the proportional growth of the head relative to the body, and the development of limbs and digits. It can be inferred that fetal development is characterized by a continuous increase in mass and a transition from simple rudimentary forms to a complex, fully formed human infant ready for birth.

Checkpoint

24. What are the general developmental trends during the fetal period?

25. Using Table 29.2 as a guide, select any one body structure in weeks 9 through 12 and trace its development through the remainder of the fetal period.

29.5 Teratogens

Objective

- Define a teratogen and provide several examples of teratogens.

Exposure of a developing embryo or fetus to certain environmental factors can damage the developing organism or even cause death. A teratogen teratojen; terato-= monster; gen = creating) is any agent or influence that causes developmental defects in the embryo. In the following sections we briefly discuss several examples.

Chemicals and Drugs

Because the placenta is not an absolute barrier between the maternal and fetal circulations, any drug or chemical that is dangerous to an infant should be considered potentially dangerous to the fetus when given to the mother. Alcohol is by far the number-one fetal teratogen. Intrauterine exposure to even a small amount of alcohol may result in fetal alcohol syndrome (F.A.S), one of the most common causes of mental retardation and the most common preventable cause of birth defects in the United States. The symptoms of F.A.S may include slow growth before and after birth, characteristic facial features (short palpebral fissures, a thin upper lip, and sunken nasal bridge), defective heart and other organs, malformed limbs, genital abnormalities, and central nervous system damage. Behavioral problems, such as hyperactivity, extreme nervousness, reduced ability to concentrate, and an inability to appreciate cause-and-effect relationships, are common.

Other teratogens include certain viruses (hepatitis B and C and certain papilloma viruses that cause sexually transmitted diseases); pesticides; defoliants (chemicals that cause plants to shed their leaves prematurely); industrial chemicals; some hormones; antibiotics; oral anticoagulants, anticonvulsants, antitumor agents, thyroid drugs, thalidomide, diethylstilbestrol, and numerous other prescription drugs; L.S.D; and cocaine. A pregnant woman who uses cocaine, for example, subjects the fetus to higher risk of retarded growth, attention and orientation problems, hyperirritability, a tendency to stop breathing, malformed or missing organs, strokes, and seizures. The risks of spontaneous abortion, premature birth, and stillbirth also increase with fetal exposure to cocaine.

Cigarette Smoking

Strong evidence implicates cigarette smoking during pregnancy as a cause of low infant birth weight; there is also a strong association between smoking and a higher fetal and infant mortality rate. Women who smoke have a much higher risk of an ectopic pregnancy. Cigarette smoke may be teratogenic and may cause cardiac abnormalities as well as anencephaly (see Clinical Connection: Anencephaly in Section 29.1). Maternal smoking also is a significant factor in the development of cleft lip and palate and has been linked with sudden infant death syndrome.

Infants nursing from smoking mothers have also been found to have an increased incidence of digestive canal disturbances. Even a mother's exposure to secondhand cigarette smoke (breathing air containing tobacco smoke) during pregnancy or while nursing predisposes her baby to increased incidence of respiratory problems, including bronchitis and pneumonia, during the first year of life.

Irradiation

Ionizing radiation of various kinds is a potent teratogen. Exposure of pregnant mothers to x-rays or radioactive isotopes during the embryo's susceptible period of development may cause microcephaly (small head size relative to the rest of the body), mental retardation, and skeletal malformations. Caution is advised, especially during the first trimester of pregnancy.

Checkpoint

29.6 Prenatal Diagnostic Tests

Several tests are available to detect genetic disorders and assess fetal well-being. Here we describe fetal ultrasonography, amniocentesis, and chorionic villi sampling.

Fetal Ultrasonography

If there is a question about the normal progress of a pregnancy, fetal ultrasonography ultrasonografe may be performed. By far the most common use of diagnostic ultrasound is to determine a more accurate fetal age when the date of conception is unclear. It is also used to confirm pregnancy, evaluate fetal viability and growth, determine fetal position, identify multiple pregnancies, identify fetal-maternal abnormalities, and serve as an adjunct to special procedures such as amniocentesis. During fetal ultrasonography, a transducer, an instrument that emits high-frequency sound waves, is passed back and forth over the abdomen. The reflected sound waves from the developing fetus are picked up by the transducer and converted to an on-screen image called a sonogram (see Table 1.3). Because the urinary bladder serves as a landmark during the procedure, the patient needs to drink liquids before the procedure and not void urine to maintain a full bladder.

Amniocentesis

Amniocentesis (am'-ně-ð-sen-TĚ-sis; amnio-= amnion; -centesis = puncture to remove fluid) involves withdrawing some of the amniotic fluid that bathes the developing fetus and analyzing the fetal cells and dissolved substances. It is used to test for the presence of certain genetic disorders, such as Down syndrome (D.S), hemophilia, Tay-Sachs disease, sickle cell disease, and certain muscular dystrophies. It is also used to help determine survivability of the fetus.

The test is usually done at 14 to 18 weeks of gestation. All gross chromosomal abnormalities and over 50 biochemical defects can be detected through amniocentesis. It can also reveal the baby's gender; this is important information for the diagnosis of sex-linked disorders, in which an abnormal gene carried by the mother affects her male offspring only (described in Section 29.12).

During amniocentesis, the position of the fetus and placenta is first identified using ultrasound and palpation. After the skin is prepared with an antiseptic and a local anesthetic is given, a hypodermic needle is inserted through the mother's abdominal wall and into the amniotic cavity within the uterus. Then, 10 to 30 mL of fluid and suspended cells are aspirated (Figure 29.15a) for microscopic examination and biochemical testing.

Elevated levels of alpha-fetoprotein (A.F.P) and acetylcholinesterase may indicate failure of the nervous system to develop properly, as occurs in spina bifida or anencephaly (absence of the cerebrum), or may be due to other developmental or chromosomal problems. Chromosome studies, which require growing the cells for 2 to 4 weeks in a culture medium, may reveal rearranged, missing, or extra chromosomes. Amniocentesis is performed only when a risk for genetic defects is suspected, because there is about a 0.5% chance of spontaneous abortion after the procedure.

Figure 29.15 Amniocentesis and Chorionic Villi Sampling.

To detect genetic abnormalities, amniocentesis is performed at 14 to 16 weeks of gestation; chorionic villi sampling may be performed as early as 8 weeks of gestation.

Figure 29.15 summary: This figure consists of two anatomical diagrams. The illustrations depict the medical procedures for amniocentesis and chorionic villi sampling. The first diagram shows a needle being guided by an ultrasound transducer through the abdominal wall and uterus to collect amniotic fluid surrounding a fetus. The second diagram illustrates chorionic villi sampling, where a needle is used to obtain a tissue sample from the chorionic villi, while also showing the relative positions of the urinary bladder and vagina. These diagrams demonstrate that both procedures utilize ultrasound guidance to ensure the safe and precise extraction of prenatal genetic material, with amniocentesis targeting the fluid and chorionic villi sampling targeting placental tissue.

Chorionic Villi Sampling

In chorionic villi sampling (C.V.S), a catheter is guided through the vagina and cervix of the uterus and then advanced to the chorionic villi under ultrasound guidance (Figure 29.15b). About 30 milligrams of tissue is suctioned out and prepared for chromosomal analysis. Alternatively, the chorionic villi can be sampled by inserting a needle through the abdominal cavity, as performed in amniocentesis.

C.V.S can identify the same defects as amniocentesis because chorion cells and fetal cells contain the same genome. C.V.S offers several advantages over amniocentesis: It can be performed as early as 8 weeks of gestation, and test results are available in only a few days, permitting an earlier decision on whether to continue the pregnancy. However, C.V.S is slightly riskier than amniocentesis; after the procedure there is a 1 to 2% chance of spontaneous abortion.

Noninvasive Prenatal Tests

Currently, chorionic villi testing and amniocentesis are the only useful ways to obtain fetal tissue for prenatal testing of gene defects. While these invasive procedures pose relatively little risk when performed by experts, much work has been done to develop noninvasive prenatal tests, which do not require the penetration of any embryonic structure. The goal is to develop accurate, safe, more efficient, and less expensive tests for screening a large population.

The first such test developed was the maternal alpha-fetoprotein (A.F.P) test alpha fetoproten. In this test, the mother's blood is analyzed for the presence of A.F.P, a protein synthesized in the fetus that passes into the maternal circulation. The highest levels of A.F.P normally occur during weeks 12 through 15 of pregnancy. Later, A.F.P is not produced, and its concentration decreases to a very low level both in the fetus and in maternal blood. A high level of A.F.P after week 16 usually indicates that the fetus has a neural tube defect, such as spina bifida or anencephaly. Because the test is 95% accurate, it is now recommended that all pregnant women be tested for A.F.P. A newer test (Quad A.F.P Plus) probes maternal blood for A.F.P and three other molecules. The test permits prenatal screening for Down syndrome, trisomy 18, and neural tube defects; it also helps predict the delivery date and may reveal the presence of twins.

Checkpoint

28. What conditions can be detected using fetal ultrasonography, amniocentesis, and chorionic villi sampling? What are the advantages of noninvasive prenatal tests?

29.7 Maternal Changes During Pregnancy

Objectives

- Describe the sources and functions of the hormones secreted during pregnancy.

• Discuss the hormonal, anatomical, and physiological changes in the mother during pregnancy.

Hormones of Pregnancy

During the first 3 to 4 months of pregnancy, the corpus luteum in the ovary continues to secrete progesterone and estrogens, which maintain the lining of the uterus during pregnancy and prepare the mammary glands to secrete milk. The amounts secreted by the corpus luteum, however, are only slightly more than those produced after ovulation in a normal menstrual cycle.

Figure 29.16 Hormones During Pregnancy.

From the third month through the remainder of the pregnancy, the placenta itself provides the high levels of progesterone and estrogens required. As noted previously, the chorion of the placenta secretes human chorionic gonadotropin (hCG) koreonik gonadotropin into the blood. In turn, hCG stimulates the corpus luteum to continue production of progesterone and estrogens—an activity required to prevent menstruation and for the continued attachment of the embryo and fetus to the lining of the uterus (Figure 29.16a). By the eighth day after fertilization, hCG can be detected in the blood and urine of a pregnant woman. Peak secretion of hCG occurs at about the ninth week of pregnancy (Figure 29.16b). During the fourth and fifth months the hCG level decreases sharply and then levels off until childbirth.

The chorion begins to secrete estrogens after the first 3 or 4 weeks of pregnancy and progesterone by the sixth week. These hormones are secreted in increasing quantities until the time of birth (Figure 29.16b). By the fourth month, when the placenta is fully established, the secretion of hCG is greatly reduced, and the secretions of the corpus luteum are no longer essential. A high level of progesterone ensures that the uterine myometrium is relaxed and that the cervix is tightly closed. After delivery, estrogens and progesterone in the blood decrease to normal levels.

The corpus luteum produces progesterone and estrogens during the first 3 to 4 months of pregnancy, after which time the placenta assumes this function.

Relaxin, a hormone produced first by the corpus luteum of the ovary and later by the placenta, increases the flexibility of the pubic symphysis and ligaments of the sacroiliac and sacrococcygeal joints and helps dilate the uterine cervix during labor. Both of these actions ease delivery of the baby.

A third hormone produced by the chorion of the placenta is human chorionic somatomammotropin (hCS) somatomamotropin, also known as human placental lactogen (hPL). The rate of secretion of hCS increases in proportion to placental mass, reaching maximum levels after 32 weeks and remaining relatively constant after that. It is thought to help prepare the mammary glands for lactation, enhance maternal growth by increasing protein synthesis, and regulate certain aspects of metabolism in both mother and fetus. For example, hCS decreases the use of glucose by the mother and promotes the release of fatty acids from her adipose tissue, making more glucose available to the fetus.

The hormone most recently found to be produced by the placenta is corticotropin-releasing hormone (C.R.H) kortikotropin, which in nonpregnant people is secreted only by neurosecretory cells in the hypothalamus. C.R.H is now thought to be part of the "clock" that establishes the timing of birth. Secretion of C.R.H by the placenta begins at about 12 weeks and increases enormously toward the end of pregnancy. Women who have higher levels of C.R.H earlier in pregnancy are more likely to deliver prematurely; those who have low levels are more likely to deliver after their due date. C.R.H from the placenta has a second important effect: It increases secretion of cortisol, which is needed for maturation of the fetal lungs and the production of surfactant (see "Pulmonary Alveoli" in Section 23.3).

Changes During Pregnancy

Near the end of the third month of pregnancy, the uterus occupies most of the pelvic cavity. As the fetus continues to grow,

Early Pregnancy Tests

Early pregnancy tests detect the tiny amounts of human chorionic gonadotropin (hCG) in the urine that begin to be excreted about 8 days after fertilization. The test kits can detect pregnancy as early as the first day of a missed menstrual period—that is, at about 14 days after fertilization. Chemicals in the kits produce a color change if a reaction occurs between hCG in the urine and hCG antibodies included in the kit.

Several of the test kits available at pharmacies are as sensitive and accurate as test methods used in many hospitals. Still, false-negative and false-positive results can occur. A false-negative result (the test is negative, but the woman is pregnant) may be due to testing too soon or to an ectopic pregnancy.

A false-positive result (the test is positive, but the woman is not pregnant) may be due to excess protein or blood in the urine or to hCG production due to a rare type of uterine cancer. Thiazide diuretics, hormones, steroids, and thyroid drugs may also affect the outcome of an early pregnancy test. the uterus extends higher and higher into the abdominal cavity. Toward the end of a full-term pregnancy, the uterus fills nearly the entire abdominal cavity, reaching above the costal margin nearly to the xiphoid process of the sternum (Figure 29.17). It pushes the maternal intestines, liver, and stomach superiorly, elevates the diaphragm, and widens the thoracic cavity. Pressure on the stomach may force the stomach contents superiorly into the esophagus, resulting in heartburn. In the pelvic cavity, compression of the ureters and urinary bladder occurs.

Figure 29.17 summary: This figure is an anatomical diagram. It illustrates the internal organs of a pregnant female, showing the spatial relationship between the enlarged uterus and other abdominal and thoracic organs. The diagram highlights the displacement of the stomach, liver, and intestines as the uterus expands to accommodate the developing fetus, while also labeling the fetal head and umbilical cord. The illustration demonstrates that during late pregnancy, the uterus occupies a significant portion of the abdominal cavity, pushing other visceral organs superiorly and laterally.

Pregnancy-induced physiological changes also occur, including weight gain due to the fetus, amniotic fluid, the placenta, uterine enlargement, and increased total body water; increased storage of proteins, triglycerides, and minerals; marked breast enlargement in preparation for lactation; and lower back pain due to lordosis (hollow back).

Several changes occur in the maternal cardiovascular system. Stroke volume increases by about 30% and cardiac output rises by 20 to 30% due to increased maternal blood flow to the placenta and increased metabolism. Heart rate increases 10 to 15% and blood volume increases 30 to 50%, mostly during the second half of pregnancy. These increases are necessary to meet the additional demands of the fetus for nutrients and oxygen.

When a pregnant woman is lying on her back, the enlarged uterus may compress the ay-or-tuh, resulting in diminished blood flow to the uterus. Compression of the inferior vena cava also decreases venous return, which leads to edema in the lower limbs and may produce varicose veins. Compression of the renal artery can lead to renal hypertension.

Respiratory function is also altered during pregnancy to meet the added oxygen demands of the fetus. Tidal volume can increase by 30 to 40%, expiratory reserve volume can be reduced by up to 40%, functional residual capacity can decline by up to 25%, minute ventilation (the total volume of air inhaled and exhaled each minute) can increase by up to 40%, airway resistance in the bronchial tree can decline by 30 to 40%, and total Figure 29.17 Normal fetal location and position at the end of a full-term pregnancy.

The gestation period is the time interval (about 38 weeks) from fertilization to birth. body oxygen consumption can increase by about 10 to 20%. Dyspnea (difficult breathing) also occurs.

The digestive system also undergoes changes. Pregnant women experience an increase in appetite due to the added nutritional demands of the fetus. A general decrease in digestive canal motility can cause constipation, delay gastric emptying time, and produce nausea, vomiting, and heartburn.

Pressure on the urinary bladder by the enlarging uterus can produce urinary symptoms, such as increased frequency and urgency of urination, and stress incontinence. An increase in renal plasma flow up to 35% and an increase in glomerular filtration rate up to 40% increase the renal filtering capacity, which allows faster elimination of the extra wastes produced by the fetus.

Changes in the skin during pregnancy are more apparent in some women than in others. Some women experience increased pigmentation around the eyes and cheekbones in a masklike pattern (chloasma), in the areolae of the breasts, and in a horizontal line along the lower abdomen called the linea nigra. Striae (stretch marks) over the abdomen can occur as the uterus enlarges, and hair loss increases.

Changes in the genital system include edema and increased vascularity of the vulva and increased pliability and vascularity of the vagina. The uterus increases from its non-pregnant mass of 60 to 80 g to 900 to 1200 g at term because of hyperplasia of muscle fibers in the myometrium in early pregnancy and hypertrophy of muscle fibers during the second and third trimesters.

Pregnancy-Induced Hypertension

About 10 to 15% of all pregnant women in the United States experience pregnancy-induced hypertension (P.I.H), an elevated blood pressure that is associated with pregnancy. The major cause is preeclampsia preeklampsia, an abnormal condition of pregnancy characterized by sudden hypertension, large amounts of protein in the urine, and generalized edema that typically appears after the 20th week of pregnancy. Other signs and symptoms are generalized edema, blurred vision, and headaches. Preeclampsia might be related to an autoimmune or allergic reaction resulting from the presence of a fetus. Treatment involves bed rest and various drugs. When the condition is also associated with convulsions and coma, it is termed eclampsia.

Checkpoint

29.8 Exercise and Pregnancy

Objective

• Explain the effects of pregnancy on exercise and of exercise on pregnancy.

Only a few changes in early pregnancy affect the ability to exercise. A pregnant woman may tire more easily than usual, or morning sickness may interfere with regular exercise. As the pregnancy progresses, weight is gained and posture changes, so more energy is needed to perform activities, and certain maneuvers (sudden stopping, changes in direction, rapid movements) are more difficult to execute. In addition, certain joints, especially the pubic symphysis, become less stable in response to the increased level of the hormone relaxin. As compensation, many mothers-to-be walk with widely spread legs and a shuffling motion.

Although blood shifts from viscera (including the uterus) to the muscles and skin during exercise, there is no evidence of inadequate blood flow to the placenta. The heat generated during exercise may cause dehydration and further increase body temperature. Especially during early pregnancy, excessive exercise and heat buildup should be avoided because elevated body temperature has been implicated in neural tube defects. Exercise has no known effect on lactation, provided a woman remains hydrated and wears a bra that provides good support. Overall, moderate physical activity does not endanger the fetus of a healthy woman who has a normal pregnancy. However, any physical activity that might endanger the fetus should be avoided.

Among the benefits of exercise to the mother during pregnancy are a greater sense of well-being and fewer physical complaints.

Checkpoint

29.9

Labor

Objective

• Explain the events associated with the three stages of labor.

Labor is the process by which the fetus is expelled from the uterus through the vagina, also referred to as giving birth. A synonym for labor is parturition parturishun; parturit-= childbirth).

The onset of labor is determined by complex interactions of several placental and fetal hormones. Because progesterone inhibits uterine contractions, labor cannot take place until the effects of progesterone are diminished. Toward the end of gestation, the levels of estrogens in the mother's blood rise sharply, producing changes that overcome the inhibiting effects of progesterone. The rise in estrogens results from increasing secretion by the placenta of corticotropin-releasing hormone, which stimulates the anterior pituitary gland of the fetus to secrete adrenocorticotropic hormone (A.C.T.H). In turn, A.C.T.H stimulates the fetal suprarenal gland to secrete cortisol and dehydroepiandrosterone (D.H.E.A) dehydroepian drosternon, the major suprarenal androgen.

The placenta then converts D.H.E.A into an estrogen. High levels of estrogens cause the number of receptors for oxytocin on uterine muscle fibers to increase, and cause uterine muscle fibers to form gap junctions with one another. Oxytocin released by the posterior pituitary stimulates uterine contractions, and relaxin from the placenta assists by increasing the flexibility of the pubic symphysis and helping dilate the uterine cervix. Estrogen also stimulates the placenta to release prostaglandins, which induce production of enzymes that digest collagen fibers in the cervix, causing it to soften.

Control of labor contractions during parturition occurs via a positive feedback cycle (see Figure 1.5). Contractions of the uterine myometrium force the baby's head or body into the cervix, distending (stretching) the cervix. Stretch receptors in the cervix send nerve impulses to neurosecretory cells in the hypothalamus, causing them to release oxytocin into blood capillaries of the posterior pituitary gland. Oxytocin then is carried by the blood to the uterus, where it stimulates the myometrium to contract more forcefully.

As the contractions intensify, the baby's body stretches the cervix still more, and the resulting nerve impulses stimulate the secretion of yet more oxytocin. With birth of the infant, the positive feedback cycle is broken because cervical distension suddenly lessens.

Uterine contractions occur in waves (quite similar to the peristaltic waves of the gastrointestinal tract) that start at the top of the uterus and move downward, eventually expelling the fetus. True labor begins when uterine contractions occur at regular intervals, usually producing pain. As the interval between contractions shortens, the contractions intensify.

Another symptom of true labor in some women is localization of pain in the back that is intensified by walking. The most reliable indicator of true labor is dilation of the cervix and the "show," a discharge of a blood-containing mucus into the cervical canal. In false labor, pain is felt in the abdomen at irregular intervals, but it does not intensify and walking does not alter it significantly. There is no "show" and no cervical dilation.

True labor can be divided into three stages (Figure 29.18):

Stage of dilation. The time from the onset of labor to the complete dilation of the cervix is the stage of dilation. This stage, which typically lasts 6 to 12 hours, features regular contractions of the uterus, usually a rupturing of the amniotic sac, and complete dilation (to 10 centimeters) of the cervix. If the amniotic sac does not rupture spontaneously, it is ruptured intentionally. ② Stage of expulsion. The time (10 minutes to several hours) from complete cervical dilation to delivery of the baby is the stage of expulsion.

3 Placental stage. The time (3 to 5 minutes or up to an hour or more) after delivery until the placenta or “afterbirth” is expelled by powerful uterine contractions is the placental stage. These contractions also constrict blood vessels that were torn during delivery, reducing the likelihood of hemorrhage.

As a rule, labor lasts longer with first babies, typically about 14 hours. For women who have previously given birth, the average duration of labor is about 8 hours—although the time varies enormously among births. Because the fetus may be squeezed through the birth canal (cervix and vagina) for up to several hours, the fetus is stressed during childbirth: The fetal head is compressed, and the fetus undergoes some degree of intermittent hypoxia due to compression of the umbilical cord and the placenta during uterine contractions. In response to this stress, the fetal adrenal medullae secrete very high levels of epinephrine and norepinephrine, the “fight-or-flight” hormones.

Much of the protection against the stresses of parturition, as well as preparation of the infant for surviving extrauterine life, is provided by these hormones. Among other functions, epinephrine and norepinephrine clear the lungs and alter their physiology in readiness for breathing air, mobilize readily usable nutrients for cellular metabolism, and promote an increased flow of blood to the brain and heart.

About 7% of pregnant women do not deliver by 2 weeks after their due date. Such cases carry an increased risk of brain damage to the fetus, and even fetal death, due to inadequate supplies of oxygen and nutrients from an aging placenta. Post-term deliveries may be facilitated by inducing labor, initiated by administration of oxytocin (Pitocin registered trademark), or by surgical delivery (cesarean section).

Following the delivery of the baby and placenta is a 6-week period during which the maternal reproductive organs and physiology return to the prepregnancy state. This period is called the puerperium puerperium. Through a process of tissue catabolism, the uterus undergoes a remarkable reduction in size, called involution involution, especially in lactating women. The cervix loses its elasticity and regains its prepregnancy firmness. For 2 to 4 weeks after delivery, women have a uterine discharge called lochia (Lo-ke-a), which consists initially of blood and later of serous fluid derived from the former site of the placenta.

Clinical Connection

Dystocia and Cesarean Section

Dystocia (dis-To-se-a; dys-= painful or difficult; -toc-= birth), or difficult labor, may result either from an abnormal position (presentation) of the fetus or a birth canal of inadequate size to permit vaginal delivery. In a breech presentation, for example, the fetal buttocks or lower limbs, rather than the head, enter the birth canal first; this occurs most often in premature births. If fetal or maternal distress prevents a vaginal birth, the baby may be delivered surgically through an abdominal incision.

A low, horizontal cut is made through the abdominal wall and lower portion of the uterus, through which the baby and placenta are removed. Even though it is popularly associated with the birth of Julius Caesar, the true reason this procedure is termed a cesarean section (C-section) is because it was described in Roman law, lex cesarea, about 600 years before Julius Caesar was born. Even a history of multiple C-sections need not exclude a pregnant woman from attempting a vaginal delivery.

Checkpoint

29.10 Adjustments of the Infant at Birth

• Explain the respiratory and cardiovascular adjustments that occur in an infant at birth.

During pregnancy, the embryo (and later the fetus) is totally dependent on the mother for its existence. The mother supplies the fetus with oxygen and nutrients, eliminates its carbon dioxide and other wastes, protects it against shocks and temperature changes, and provides antibodies that confer protection against certain harmful microbes. At birth, a physiologically mature baby becomes much more self-supporting, and the newborn's body systems must make various adjustments. The most dramatic changes occur in the respiratory and cardiovascular systems.

Respiratory Adjustments

The reason that the fetus depends entirely on the mother for obtaining oxygen and eliminating carbon dioxide is that the fetal lungs are either collapsed or partially filled with amniotic fluid. The production of surfactant begins by the end of the sixth month of development. Because the respiratory system is fairly well developed at least 2 months before birth, premature babies delivered at 7 months are able to breathe and cry. After delivery, the baby's supply of oxygen from the mother ceases, and any amniotic fluid in the fetal lungs is absorbed. Because carbon dioxide is no longer being removed, it builds up in the blood.

A rising C-O 2 level stimulates the respiratory center in the medulla oblongata, causing the respiratory muscles to contract, and the baby to draw his or her first breath. Because the first inspiration is unusually deep, as the lungs contain no air, the baby also exhales vigorously and naturally cries. A full-term baby may breathe 45 times a minute for the first 2 weeks after birth.

Breathing rate gradually declines until it approaches a normal rate of about 12 breaths per minute.

Cardiovascular Adjustments

After the baby's first inspiration, the cardiovascular system must make several adjustments (see Figure 21.31). Closure of the foramen ovale between the atria of the fetal heart, which occurs shortly after birth, diverts deoxygenated blood to the lungs for the first time. The foramen ovale is closed by two flaps of septal heart tissue that fold together and permanently fuse. The remnant of the foramen ovale is the fossa ovalis.

Once the lungs begin to function, the ductus arteriosus shuts off due to contractions of smooth muscle in its wall, and it becomes the ligamentum arteriosum. The muscle contraction is probably mediated by the polypeptide bradykinin, released from the lungs during their initial inflation. The ductus arteriosus generally begins to close 12 to 24 hours after birth and is usually completed by 21 days after birth. Prolonged incomplete closure results in a condition called patent ductus arteriosus (see Figure 20.23b).

After the umbilical cord is tied off and severed and blood no longer flows through the umbilical arteries, they fill with connective tissue, and become the medial umbilical ligaments. The umbilical vein then becomes the ligamentum teres (round ligament) of the liver.

In the fetus, the ductus venosus connects the umbilical vein directly with the inferior vena cava, allowing blood from the placenta to bypass the fetal liver. When the umbilical cord is severed, the ductus venosus collapses, and venous blood from the viscera of the fetus flows into the hepatic portal vein to the liver and then via the hepatic vein to the inferior vena cava. The remnant of the ductus venosus becomes the ligamentum venosum.

At birth, an infant's pulse may range from 120 to 160 beats per minute and may go as high as 180 on excitation. After birth, oxygen use increases, which stimulates an increase in the rate of red blood cell and hemoglobin production. The white blood cell count at birth is very high—sometimes as much as 45,000 cells per microliter—but the count decreases rapidly by the seventh day. Recall that the white blood cell count of an adult is 5000 to 10,000 cells per microliter.

Clinical Connection

Premature Infants

Delivery of a physiologically immature baby carries certain risks. A premature infant or “preemie” is generally considered a baby who weighs less than 2500 g (5.5 pounds) at birth. Poor prenatal care, drug abuse, history of a previous premature delivery, and mother's age below 16 or above 35 increase the chance of premature delivery. The body of a premature infant is not yet ready to sustain some critical functions, and thus its survival is uncertain without medical intervention.

The major problem after delivery of an infant under 36 weeks of gestation is respiratory distress syndrome of the newborn due to insufficient surfactant. R.D.S can be eased by use of artificial surfactant and a ventilator that delivers oxygen until the lungs can operate on their own.

Checkpoint

35. Why are respiratory and cardiovascular adjustments so important at birth?

29.11 The Physiology of Lactation

Objective

• Discuss the physiology and hormonal control of lactation.

Lactation (lak-TÃ-shun) is the production and ejection of milk from the mammary glands. A principal hormone in promoting milk production is prolactin P.R.L, which is secreted from the anterior pituitary gland. Even though prolactin levels increase as the pregnancy progresses, no milk production occurs because progesterone inhibits the effects of prolactin. After delivery, the levels of estrogens and progesterone in the mother's blood decrease, and the inhibition is removed. The principal stimulus in maintaining prolactin secretion during lactation is the sucking action of the infant. Suckling initiates nerve impulses from stretch receptors in the nipples to the hypothalamus; the impulses decrease hypothalamic release of prolactin-inhibiting hormone (P.I.H) and increase release of prolactin-releasing hormone (P.R.H), so more prolactin is released by the anterior pituitary.

Oxytocin causes release of milk into the mammary ducts via the milk ejection reflex (Figure 29.19). Milk formed by the glandular alveoli of the breasts is stored until the baby begins active suckling. Stimulation of touch receptors in the nipple initiates sensory nerve impulses that are relayed to the hypothalamus. In response, secretion of oxytocin from the posterior pituitary increases.

Figure 29.19 summary: This figure is a flow chart illustrating a biological feedback loop. It describes the process of milk ejection, starting with a baby suckling on a nipple, which triggers touch sensations. These sensations are detected by receptors in the nipple, sending nerve impulses to the control center consisting of the hypothalamus and posterior pituitary. This results in an increase of oxytocin in the blood, which acts on the effectors, specifically the myoepithelial cells in the mammary glands. The contraction of these cells leads to the response of milk ejection. The process concludes with the interruption of the cycle when the baby ceases to suckle. The figure demonstrates a positive feedback mechanism where milk availability encourages continued suckling, thereby sustaining the release of oxytocin and the ejection of milk until the stimulus is removed.

Carried by the bloodstream to the mammary glands, oxytocin stimulates contraction of myoepithelial (smooth muscle-like) cells surrounding the glandular alveoli and ducts. The resulting compression moves the milk from the glandular alveoli of the mammary glands into the mammary ducts, where it can be suckled. This process is termed milk ejection (let-down). Even though the actual ejection of milk does not occur until 30 to 60 seconds after nursing begins (the latent period), some milk stored in lactiferous sinuses near the nipple is available during the latent period.

Stimuli other than suckling, such as hearing a baby's cry or touching the mother's genitals, also can trigger oxytocin release and milk ejection. The suckling stimulation that produces the release of oxytocin also inhibits the release of P.I.H; this results in increased secretion of prolactin, which maintains lactation.

During late pregnancy and the first few days after birth, the mammary glands secrete a cloudy fluid called colostrum. Although it is not as nutritious as milk—it contains less lactose and virtually no fat—colostrum serves adequately until the appearance of true milk on about the fourth day. Colostrum and maternal milk contain important antibodies that protect the infant during the first few months of life.

Following birth of the infant, the prolactin level starts to return to the nonpregnant level. However, each time the mother nurses the infant, nerve impulses from the nipples to the hypothalamus increase the release of P.R.H (and decrease the release of P.I.H), resulting in a tenfold increase in prolactin secretion by the anterior pituitary that lasts about an hour. Prolactin acts on the mammary glands to provide milk for the next nursing period. If this surge of prolactin is blocked by injury or disease, or if nursing is discontinued, the mammary glands lose their ability to produce milk in only a few days. Even though milk production normally decreases considerably within 7 to 9 months after birth, it can continue for several years if breastfeeding (nursing) continues.

Lactation often blocks ovarian cycles for the first few months following delivery, if the frequency of sucking is about 8 to 10 times a day. This effect is inconsistent, however, and ovulation commonly precedes the first menstrual period after delivery of a baby. As a result, the mother can never be certain she is not fertile. Breastfeeding is therefore an unreliable birth

Figure 29.19 The Milk Ejection Reflex, a Positive Feedback Cycle.

Oxytocin stimulates contraction of myoepithelial cells in the breasts, which squeezes the glandular and duct cells and causes milk ejection. control measure. The suppression of ovulation during lactation is believed to occur as follows: During breastfeeding, neural input from the nipple reaches the hypothalamus and causes it to produce neurotransmitters that suppress the release of gonadotropin-releasing hormone (GnRH). As a result, production of L.H and F.S.H decreases, and ovulation is inhibited.

A primary benefit of breastfeeding is nutritional: Human milk is a sterile solution that contains amounts of fatty acids, lactose, amino acids, minerals, vitamins, and water that are ideal for the baby's digestion, brain development, and growth. Breastfeeding also benefits infants by providing the following:

• Beneficial cells. Several types of white blood cells are present in breast milk. Neutrophils and macrophages serve as phagocytes, ingesting microbes in the baby's digestive canal. Macrophages also produce lysozyme and other immune system components. Plasmocytes, which develop from B lymphocytes, produce antibodies against specific microbes, and T lymphocytes kill microbes directly or help mobilize other defenses.

• Beneficial molecules. Breast milk also contains an abundance of beneficial molecules. Maternal IgA antibodies in breast milk bind to microbes in the baby's gastrointestinal tract and prevent their migration into other body tissues. Because a mother produces antibodies to whatever disease-causing microbes are present in her environment, her breast milk affords protection against the specific infectious agents to which her baby is also exposed. Additionally, two milk proteins bind to nutrients that many bacteria need to grow and survive: B _{12} -binding protein ties up vitamin B _{12} , and lactoferrin ties up iron. Some fatty acids can kill certain viruses by disrupting their membranes, and lysozyme kills bacteria by disrupting their cell walls. Finally, interferons enhance the antimicrobial activity of immune cells.

• Decreased incidence of diseases later in life. Breastfeeding provides children with a slight reduction in risk of lymphoma, heart disease, allergies, respiratory and digestive canal infections, ear infections, diarrhea, diabetes mellitus, and meningitis.

• Miscellaneous benefits. Breastfeeding supports optimal infant growth, enhances intellectual and neurological development, and fosters mother-infant relations by establishing early and prolonged contact between them. Compared to cow's milk, the fats and iron in breast milk are more easily absorbed, the proteins in breast milk are more readily metabolized, and the lower sodium content of breast milk is more suited to an infant's needs. Premature infants benefit even more from breast-feeding because the milk produced by mothers of premature infants seems to be specially adapted to the infant's needs; it has a higher protein content than the milk of mothers of full-term infants. Finally, a baby is less likely to have an allergic reaction to its mother's milk than to milk from another source.

Years before oxytocin was discovered, it was common practice in midwifery to let a first-born twin nurse at the mother's breast to speed the birth of the second child. Now we know why this practice is helpful—it stimulates the release of oxytocin. Even after a single birth, nursing promotes expulsion of the placenta (afterbirth) and helps the uterus return to its normal size. Synthetic oxytocin (Pitocin) is often given to induce labor or to increase uterine tone and control hemorrhage just after parturition.

36. Which hormones contribute to lactation? What is the function of each?

37. What are the benefits of breast-feeding over bottle-feeding?

29.12 Inheritance

Objective

• Explain the inheritance of dominant, recessive, complex, and sex-linked traits.

As previously indicated, the genetic material of a father and a mother unite when a sperm fuses with a secondary oocyte to form a zygote. Children resemble their parents because they inherit traits passed down from both parents. We now examine some of the principles involved in that process, called inheritance.

Inheritance is the passage of hereditary traits from one generation to the next. It is the process by which you acquired your characteristics from your parents and may transmit some of your traits to your children. The branch of biology that deals with inheritance is called genetics genetiks. The area of health care that offers advice on genetic problems (or potential problems) is called genetic counseling.

Genotype and Phenotype

As you have already learned, the nuclei of all human cells except gametes contain 23 pairs of chromosomes—the diploid number (2n). One chromosome in each pair came from the mother, and the other came from the father. Each of these two homologues contains genes that control the same traits. If one chromosome of the pair contains a gene for body hair, for example, its homologue will contain a gene for body hair in the same position.

Alternative forms of a gene that code for the same trait and are at the same location on homologous chromosomes are called alleles alelz. One allele of the previously mentioned body hair gene might code for coarse hair, and another might code for fine hair. A mutation (mü-TÄ-shun; muta-= change) is a permanent heritable change in an allele that produces a different variant of the same trait.

The relationship of genes to heredity is illustrated by examining the alleles involved in a disorder called phenylketonuria (P.K.U) fenilketonurea. People with P.K.U (see Clinical Connection: Phenylketonuria in Section 25.5) are unable to manufacture the enzyme phenylalanine hydroxylase. The allele that codes for phenylalanine hydroxylase is symbolized as P; the mutated allele that fails to produce a functional enzyme is represented by p. The chart in Figure 29.20, which shows the possible combinations of gametes from two parents who each have one P and one p allele, is called a Punnett square. In constructing a Punnett square, the possible paternal alleles in sperm are written at the left side and the possible maternal alleles in ova (or secondary oocytes) are written at the top. The four spaces on the chart show how the alleles can combine in zygotes formed by the union of these sperm and ova to produce the three different combinations of genes, or genotypes (JÊ-nô-tips): P.P, Pp, or pp. Notice from the Punnett square that 25% of the offspring will have the P.P genotype, 50% will have the Pp genotype, and 25% will have the pp genotype. (These percentages are probabilities only; parents who have four children won't necessarily end up with one with P.K.U.) People who inherit P.P or Pp genotypes do not have P.K.U; those with a pp genotype suffer from the disorder.

Figure 29.20 summary: This figure is a Punnett square diagram illustrating genetic inheritance. It depicts the process of meiosis in heterozygous parents, showing how different alleles from a father's sperm and a mother's ova combine to form zygotes. The diagram outlines the resulting genotypes of the offspring, categorizing them as homozygous dominant, heterozygous dominant, or homozygous recessive. Based on these genotypes, the figure concludes that offspring with dominant alleles will not have PKU, while those with the homozygous recessive genotype will express the PKU phenotype.

Figure 29.20 Inheritance of Phenylketonuria (P.K.U).

Genotype refers to genetic makeup; phenotype refers to the physical or outward expression of a gene.

If parents have the genotypes shown here, what is the chance that their first child will have P.K.U? What is the chance of P.K.U occurring in their second child?

Although people with a Pp genotype have one P.K.U allele (p), the allele that codes for the normal trait (P) masks the presence of the P.K.U allele. An allele that dominates or masks the presence of another allele and is fully expressed (P in this example) is said to be a dominant allele, and the trait expressed is called a dominant trait. The allele whose presence is completely masked (p in this example) is said to be a recessive allele, and the trait it controls is called a recessive trait.

By tradition, the symbols for genes are written in italics, with dominant alleles written in capital letters and recessive alleles in lowercase letters. A person with the same alleles on homologous chromosomes (for example, P.P or pp) is said to be homozygous (ho-mo-Zi-gus) for the trait. P.P is homozygous dominant, and pp is homozygous recessive. An individual with different alleles on homologous chromosomes (for example, Pp) is said to be heterozygous (het'-er-o-Zi-gus) for the trait.

Phenotype (Fe-no-tip; pheno-= showing) refers to how the genetic makeup is expressed in the body; it is the physical or outward expression of a gene. A person with Pp (a heterozygote) has a different genotype from a person with P.P (a homozygote), but both have the same phenotype—normal production of phenylalanine hydroxylase. Heterozygous individuals who carry a recessive gene but do not express it (Pp) can pass the gene on to their offspring. Such individuals are called carriers of the recessive gene.

Most genes give rise to the same phenotype whether they are inherited from the mother or the father. In a few cases, however, the phenotype is dramatically different, depending on the parental origin. This surprising phenomenon, first appreciated in the 1980s, is called genomic imprinting. In humans, the abnormalities most clearly associated with mutation of an imprinted gene are Angelman syndrome (mental retardation, ataxia, seizures, and minimal speech), which results when the gene for a particular abnormal trait is inherited from the mother, and Prader-Willi syndrome (short stature, mental retardation, obesity, poor responsiveness to external stimuli, and sexual immaturity), which results when it is inherited from the father.

Alleles that code for normal traits do not always dominate over those that code for abnormal ones, but dominant alleles for severe disorders usually are lethal and cause death of the embryo or fetus. One exception is Huntington disease (H.D) (see Clinical Connection: Disorders of the Basal Nuclei in Section 16.4), which is caused by a dominant allele with effects that are not manifested until adulthood. Both homozygous dominant and heterozygous people exhibit the disease; homozygous recessive people are normal. H.D causes progressive degeneration of the nervous system and eventual death, but because symptoms typically do not appear until after age 30 or 40, many afflicted individuals will already have passed on the allele for the condition to their children by the time they discover they have the disease.

Occasionally an error in cell division, called nondisjunction nondisjunkshun, results in an abnormal number of chromosomes. In this situation, homologous chromosomes (during meiosis 1) or sister chromatids (during anaphase of mitosis or meiosis 2) fail to separate properly. See Figure 3.34. A cell from which one or more chromosomes has been added or deleted is called an aneuploid anuploid. A monosomal cell (2n-1) is missing a chromosome; a trisomic cell (2n+1) has an extra chromosome. Most cases of Down syndrome (see Disorders: Homeostatic Imbalances at the end of this chapter) are aneuploid disorders in which there is trisomy of chromosome 21. Nondisjunction usually occurs during gametogenesis (meiosis), but about 2% of Down syndrome cases result from nondisjunction during mitotic divisions in early embryonic development.

Another error in meiosis is a translocation. In this case, two chromosomes that are not homologous break and interchange portions. The individual who has a translocation may be perfectly normal if no loss of genetic material took place when the rearrangement occurred. However, some of the person's gametes may not contain the correct amount and type of genetic material. About 3% of Down syndrome cases result from a translocation of part of chromosome 21 to another chromosome, usually chromosome 14 or 15. The individual who has this translocation is normal and does not even know that he or she is a "carrier." When such a carrier produces gametes, however, some gametes end up with a whole chromosome 21 plus another chromosome with the translocated fragment of chromosome 21. On fertilization, the zygote then has three, rather than two, copies of that part of chromosome 21.

Table 29.3 lists some dominant and recessive inherited structural and functional traits in humans.

Table 29.3 summary: This table lists various hereditary human traits, categorizing them by whether the condition or characteristic is governed by a dominant or recessive allele. It contrasts specific phenotypes, such as various digit abnormalities and certain medical conditions, against their normal counterparts to illustrate the inheritance patterns of these selected traits.

Variations on Dominant-Recessive Inheritance

Most patterns of inheritance do not conform to the simple dominant-recessive inheritance we have just described, in which only dominant and recessive alleles interact. The phenotypic expression of a particular gene may be influenced not only by which alleles are present, but also by other genes and by the environment. Most inherited traits are influenced by more than one gene, and, to complicate matters, most genes can influence more than one trait. Variations on dominant-recessive inheritance include incomplete dominance, multiple-allele inheritance, and complex inheritance.

Incomplete Dominance In incomplete dominance, neither member of a pair of alleles is dominant over the other, and the heterozygote has a phenotype intermediate between the homozygous dominant and the homozygous recessive phenotypes. An example of incomplete dominance in humans is the inheritance of sickle cell disease S.C.D (Figure 29.21). People with the homozygous dominant genotype Hb superscript A.H.b superscript A form normal hemoglobin; those with the homozygous recessive genotype Hb superscript S.H.b superscript S have sickle cell disease and severe anemia. Although they are usually healthy, those with the heterozygous genotype Hb superscript A.H.b superscript S have minor problems with anemia because half of their hemoglobin is normal and half is not. Heterozygotes are carriers, and they are said to have sickle cell trait.

Figure 29.21 summary: This figure is a biological diagram featuring a Punnett square. The illustration depicts the process of meiosis in parents who are heterozygous for hemoglobin alleles, showing the separation of alleles into sperm and ova. The Punnett square then maps the possible combinations of these alleles during fertilization to determine the genotypes of the resulting zygotes. Based on the diagram, offspring can inherit a combination of alleles that results in a normal genotype, a carrier genotype, or a genotype associated with sickle cell anemia, demonstrating how recessive traits can be passed from parents to children.

Multiple-Allele Inheritance Although a single individual inherits only two alleles for each gene, some genes may have more than two alternative forms; this is the basis for multiple-allele inheritance. One example of multiple-allele inheritance is the inheritance of the A.B.O blood group. The four blood types (phenotypes) of the A.B.O group—A, B, A.B, and O—result from the inheritance of six combinations of three different alleles of a single gene called the / gene: (1) allele / ^{A} produces the A antigen, (2) allele / ^{B} produces the B antigen, and (3) allele / ^{A} produces the A antigen.

Figure 29.21 Inheritance of Sickle Cell Disease.

Sickle cell disease is an example of incomplete dominance.

Hemoglobin A superscript A hemoglobin S superscript S H b with superscript s, H b with superscript s i produces neither A nor B antigen. Each person inherits two I-gene alleles, one from each parent, that give rise to the various phenotypes. The six possible genotypes produce four blood types, as follows:

Table summary: The table illustrates the relationship between specific genetic combinations and their corresponding ABO blood group phenotypes, showing how different alleles determine whether an individual has blood type A, B, AB, or O.

Notice that both I superscript A and I superscript B are inherited as dominant alleles, and i is inherited as a recessive allele. Because an individual with type A.B blood has characteristics of both type A and type B red blood cells expressed in the phenotype, alleles I superscript A and I superscript B are said to be codominant. In other words, both genes are expressed equally in the heterozygote. Depending on the parental blood types, different offspring may have blood types different from each other. Figure 29.22 shows the blood types offspring could inherit, given the blood types of their parents.

Figure 29.22 summary: The table illustrates various parental blood type combinations and the resulting possible blood types for their offspring, demonstrating how children can inherit blood types different from their parents, including the possibility of a child having type O blood when neither parent does.

Complex Inheritance Most inherited traits are not controlled by one gene, but instead by the combined effects of two or more genes, a situation referred to as polygenic inheritance polejanik; poly-= many), or the combined effects of many genes and environmental factors, a situation referred to as complex inheritance. Examples of complex traits include skin color, hair color, eye color, height, metabolism rate, and body build. In complex inheritance, one genotype can have many possible phenotypes, depending on the environment, or one phenotype can include many possible genotypes. For example, even though a person inherits several genes for Figure 29.22 The 10 possible combinations of parental A.B.O blood types and the blood types their offspring could inherit. For each possible set of parents, the blue letters represent the blood types their offspring could inherit.

Inheritance of A.B.O blood types is an example of multiple-allele inheritance. tallness, full height potential may not be reached due to environmental factors, such as disease or malnutrition during the growth years. You have already learned that the risk of having a child with a neural tube defect is greater in pregnant women who lack adequate folic acid in their diet; this is also considered an environmental factor. Because neural tube defects are more prevalent in some families than in others, however, one or more genes may also contribute.

Often, a complex trait shows a continuous gradation of small differences between extremes among individuals. It is relatively easy to predict the risk of passing on an undesirable trait that is due to a single dominant or recessive gene, but it is very difficult to make this prediction when the trait is complex. Such traits are difficult to follow in a family because the range of variation is large, the number of different genes involved usually is not known, and the impact of environmental factors may be incompletely understood.

Skin color is a good example of a complex trait. It depends on environmental factors such as sun exposure and nutrition, as well as on several genes. Suppose that skin color is controlled by three separate genes, each having two alleles: A, a; B, b; and C, c (Figure 29.23). A person with the genotype A.A.B.B.C.C is very dark skinned, an individual with the genotype aabbcc is very light skinned, and a person with the genotype AaBbCc has an intermediate skin color. Parents having an intermediate skin color may have children with very light, very dark, or intermediate skin color. Note that the P generation (parental generation) is the starting generation, the F 1 generation (first filial generation) is produced from the P generation, and the F 2 generation (second filial generation) is produced from the F 1 generation.

Figure 29.23 summary: This figure is a Punnett square diagram illustrating a genetic cross. It depicts the inheritance pattern of skin color starting from a parental generation consisting of individuals with opposing extreme phenotypes, one very dark and one very light. The first filial generation results in offspring with an intermediate phenotype. The diagram then shows the cross between these intermediate offspring, mapping out the possible combinations of ova and sperm to determine the potential genotypes and phenotypes of the second filial generation. The resulting grid of offspring demonstrates a wide spectrum of skin tones. While some offspring maintain the intermediate shade, others exhibit phenotypes that lean toward the extremes of the parental generation. This distribution indicates that the trait is controlled by multiple genes acting additively, leading to a continuous variation of skin color rather than a simple dominant or recessive pattern.

Autosomes, Sex Chromosomes, and Sex Determination

When viewed under a microscope, the 46 human chromosomes in a normal somatic cell can be identified by their size, shape, and staining pattern to be members of 23 different pairs. An entire set of chromosomes arranged in decreasing order of size and according to the position of the centromere is called a karyotype karyotip; karyo-= nucleus; -typos = model) (Figure 29.24). In 22 of the pairs, the homologous chromosomes look alike and have the same appearance in both males and females; these 22 pairs are called autosomes autosoms. The two members of the 23rd pair are termed the sex chromosomes; they look different in males and females. In females, the pair consists of two chromosomes called X chromosomes. One X chromosome is also present in males, but its mate is a much smaller chromosome called a Y chromosome. The Y chromosome has only 231 genes, less than 10% of the 2968 genes present on chromosome 1, the largest autosome.

Figure 29.24 summary: This figure is a karyotype diagram. It displays the complete set of human chromosomes arranged in numbered pairs, including the sex chromosomes. The image illustrates that human somatic cells possess a specific number of chromosome pairs that decrease in size from the first pair to the twenty-second pair, concluding with the distinct X and Y chromosomes that determine biological sex.

When a spermatocyte undergoes meiosis to reduce its chromosome number, it gives rise to two sperm that contain an X chromosome and two sperm that contain a Y chromosome. Oocytes have no Y chromosomes and produce only X-containing gametes. If the secondary oocyte is fertilized by an X-bearing sperm, the offspring normally is female (20). Fertilization by a Y-bearing sperm produces a male (X.Y). Thus, an individual's sex is determined by the father's chromosomes (Figure 29.25).

Both female and male embryos develop identically until about 7 weeks after fertilization. At that point, one or more genes set into motion a cascade of events that leads to the development of a male; in the absence of normal expression of the gene or genes, the female pattern of development occurs. It has been known since 1959 that the Y chromosome is needed to initiate male development. Experiments published in 1991 established that the prime male-determining gene is one called S.R.Y (sex-determining region of the Y chromosome). When a small D.N.A fragment containing this gene was inserted into 11 female mouse embryos, three of them developed as males. (The researchers suspected that the gene failed to be integrated into the genetic material in the other eight.) S.R.Y acts as a molecular switch to turn on the male pattern of development. Only if the S.R.Y gene is present and functional in a fertilized ovum will the fetus develop testes and differentiate into a male; in the absence of S.R.Y, the fetus will develop ovaries and differentiate into a female.

Case studies have confirmed the key role of S.R.Y in directing the male pattern of development in humans. In some cases, phenotypic females with an X.Y genotype were found to have mutated S.R.Y genes. These individuals failed to develop normally as males because their S.R.Y gene was defective. In other cases, phenotypic males with an X.X genotype were found to have a small piece of the Y chromosome, including the S.R.Y gene, inserted into one of their X chromosomes.

Sex-Linked Inheritance

In addition to determining the sex of the offspring, the sex chromosomes are responsible for the transmission of several nonsexual traits. Many of the genes for these traits are present on X chromosomes but are absent from Y chromosomes. This feature produces a pattern of heredity called sex-linked inheritance that is different from the patterns already described.

Red-Green Color Blindness One example of sex-linked inheritance is red-green color blindness, the most common type of color blindness. This condition is characterized by a deficiency in either red-or green-sensitive cones, so red and green are seen as the same color (either red or green, depending on which cone is present). The gene for red-green color blindness is a recessive one designated c. Normal color vision, designated C, dominates. The C/c genes are located only on the X chromosome, so the ability to see colors depends entirely on the X chromosomes. The possible combinations are as follows:

Table summary: The table illustrates the relationship between specific genotypes and the resulting phenotypes for red-green color blindness in both males and females, demonstrating how different combinations of sex chromosomes lead to either normal vision or color blindness.

Only females who have two Xc genes are red-green color blind. This rare situation can result only from the mating of a color-blind male and a color-blind or carrier female. Because males do not have a second X chromosome that could mask the trait, all males with an Xc gene will be red-green color blind. Figure 29.26 illustrates the inheritance of red-green color blindness in the offspring of a normal male and a carrier female.

Figure 29.26 summary: This figure is a diagram featuring Punnett squares used to illustrate genetic inheritance. The content depicts the process of meiosis and fertilization between a normal male and a normal female who is a carrier of a recessive gene for red-green color blindness. It shows the possible combinations of sex chromosomes and alleles from the sperm and ova that form the genotypes of the resulting zygotes. The diagram demonstrates that offspring can be normal females, carrier females, normal males, or color-blind males. It can be inferred that the recessive trait for color blindness is sex-linked, meaning it is carried on the X chromosome. Because males possess only one X chromosome, they are more likely to express the phenotype if they inherit the recessive allele from their mother, whereas females must inherit two copies of the recessive allele to be color-blind or one copy to be a carrier.

Traits inherited in the manner just described are called sex-linked traits. The most common type of hemophilia hemofilia—a condition in which the blood fails to clot or clots very slowly after an injury—is also a sex-linked trait. Like the trait for red-green color blindness, hemophilia is caused by a recessive gene. Other sex-linked traits in humans are fragile X syndrome, nonfunctional sweat glands, certain forms of diabetes, some types of deafness, uncontrollable rolling of the eyeballs, absence of central incisors, night blindness, one form of cataract, juvenile glaucoma, and juvenile muscular dystrophy.

X-Chromosome Inactivation Because they have two X chromosomes in every cell (except developing oocytes), females have a double set of all genes on the X chromosome. A mechanism termed X-chromosome inactivation (lyonization) in effect reduces the X-chromosome genes to a single set in females. In each cell of a female's body, one X chromosome is randomly and permanently inactivated early in development, and most of the genes of the inactivated X chromosome are not expressed (transcribed and translated). The nuclei of cells in female mammals contain a dark-staining body, called a Barr body, that is not present in the nuclei of cells in males. Geneticist Mary Lyon correctly predicted in 1961 that the Barr body is the inactivated X chromosome. During inactivation, chemical groups that prevent transcription into R.N.A are added to the X chromosome's D.N.A. As a result, an inactivated X chromosome reacts differently to histological stains and has a different appearance than the rest of the D.N.A. In nondividing (interphase) cells, it remains tightly coiled and can be seen as a dark-staining body within the nucleus. In a blood smear, the Barr body of neutrophils is termed a "drumstick" because it looks like a tiny drumstick-shaped projection of the nucleus.

Checkpoint

42. Define complex inheritance and give an example.

43. Why does X-chromosome inactivation occur?

Disorders: Homeostatic Imbalances

Infertility

Female infertility, or the inability to conceive, occurs in about 10% of all women of reproductive age in the United States.

Female infertility may be caused by ovarian disease, obstruction of the uterine tubes, or conditions in which the uterus is not adequately prepared to receive a fertilized ovum. Male infertility (sterility) occurs in about 10% of males in the United States and is defined as an inability to fertilize a secondary oocyte; it does not imply erectile dysfunction (impotence). Male fertility requires production of adequate quantities of viable, normal sperm by the testes, unobstructed transport of sperm though the ducts, and satisfactory deposition in the vagina. The seminiferous tubules of the testes are sensitive to many factors—x-rays, infections, toxins, malnutrition, and higher-than-normal scrotal temperatures—that may cause degenerative changes and produce male sterility.

One cause of infertility in females is inadequate body fat. To begin and maintain a normal reproductive cycle, a female must have a minimum amount of body fat. Even a moderate deficiency of fat—10% to 15% below normal weight for height—may delay the onset of menstruation (menarche), inhibit ovulation during the genital cycle, or cause amenorrhea (cessation of menstruation). Both dieting and intensive exercise may reduce body fat below the minimum amount and lead to infertility that is reversible, if weight gain or reduction of intensive exercise or both occur.

Studies of very obese women indicate that they, like very lean ones, experience problems with amenorrhea and infertility. Males also experience genital problems in response to undernutrition and weight loss. For example, they produce less prostatic fluid and reduced numbers of sperm having decreased motility.

Many fertility-expanding techniques now exist for assisting infertile couples to have a baby. The birth of Louise Joy Brown on July 12, 1978, near Manchester, England, was the first recorded case of in vitro fertilization (I.V.F)—fertilization in a laboratory dish. In the I.V.F procedure, the mother-to-be is given follicle-stimulating hormone (F.S.H) soon after menstruation, so that several secondary oocytes, rather than the typical single oocyte, will be produced (superovulation). When several follicles have reached the appropriate size, a small incision is made near the umbilicus, and the secondary oocytes are aspirated from the stimulated follicles and transferred to a solution containing sperm, where the oocytes undergo fertilization.

Alternatively, an oocyte may be fertilized in vitro by suctioning a sperm or even a spermatid obtained from the testis into a tiny pipette and then injecting it into the oocyte's cytoplasm. This procedure, termed intracytoplasmic sperm injection I.C.S.I intrasitoplazmik, has been used when infertility is due to impairments in sperm motility or to the failure of spermatids to develop into spermatozoa. When the zygote achieved by I.V.F reaches the 8-cell or 16-cell stage, it is introduced into the uterus for implantation and subsequent growth.

In embryo transfer, a man's semen is used to artificially inseminate a fertile secondary oocyte donor. After fertilization in the donor's uterine tube, the morula or blastocyst is transferred from the donor to the infertile woman, who then carries it (and subsequently the fetus) to term. Embryo transfer is indicated for women who are infertile or who do not want to pass on their own genes because they are carriers of a serious genetic disorder.

In gamete intrafallopian transfer gift the goal is to mimic the normal process of conception by uniting sperm and secondary oocyte in the prospective mother's uterine tubes. It is an attempt to bypass conditions in the female genital tract that might prevent fertilization, such as high acidity or inappropriate mucus. In this procedure, a woman is given F.S.H and L.H to stimulate the production of several secondary oocytes, which are aspirated from the mature ovarian follicles, mixed outside the body with a solution containing sperm, and then immediately inserted into the uterine tubes.

Congenital Defects

An abnormality that is present at birth, and usually before, is called a congenital defect. Such defects occur during the formation of structures that develop during the period of organogenesis, the fourth through eighth weeks of development, when all major organs appear. During organogenesis, stem cells are establishing the basic patterns of organ development, and it is during this time that developing structures are very susceptible to genetic and environmental influences.

Major structural defects occur in 2 to 3% of liveborn infants, and they are the leading cause of infant mortality, accounting for about 21% of infant deaths. Many congenital defects can be prevented by supplementation or avoidance of certain

Medical Terminology

Breech presentation A malpresentation in which the fetal buttocks or lower limbs present into the maternal pelvis; the most common cause is prematurity.

Conceptus konseptus Includes all structures that develop from a zygote and includes an embryo plus the embryonic part of the placenta and associated membranes (chorion, amnion, umbilical vesicle, and allantois).

Cryopreserved embryo kriopreservd; cryo-= cold) An early embryo produced by in vitro fertilization (fertilization of a secondary oocyte in a laboratory dish) that is preserved for a long period by freezing it. After thawing, the early embryo is implanted into the uterine cavity. Also called a frozen embryo.

Deformation (dê-for-MÃ-shun; de-= without; -forma = form) A developmental abnormality due to mechanical strains that mold a part of the fetus over a prolonged period of time. Deformations usually involve the skeletal and/or muscular system and may be corrected after birth. An example is clubfeet.

Emesis gravidarum emesis gravidarum; emeo = to vomit; gravida = a pregnant woman | Episodes of nausea and possibly vomiting that are most likely to occur in the morning during the early weeks of pregnancy; also called morning sickness. Its cause is unknown, but the high levels of human chorionic gonadotropin secreted by the placenta, and of progesterone secreted by the ovaries, have been implicated. If the severity of these symptoms requires hospitalization for intravenous feeding, the condition is known as hyperemesis gravidarum. epienesis; epi-= upon; -genesis = creation) The development of an organism from an undifferentiated cell. substances. For example, neural tube defects, such as spina bifida and anencephaly, can be prevented by having a pregnant female take folic acid. Iodine supplementation can prevent the mental retardation and bone deformation associated with cretinism. Avoidance of teratogens is also very important in preventing congenital defects.

Down Syndrome

Down syndrome (D.S) is a disorder characterized by three, rather than two, copies of at least part of chromosome 21. Overall, one infant in 900 is born with Down syndrome. However, older women are more likely to have a D.S baby. The chance of having a baby with this syndrome, which is less than 1 in 3000 for women under age 30, increases to 1 in 300 in the 35 to 39 age group and to 1 in 9 at age 48.

Down syndrome is characterized by mental retardation, retarded physical development (short stature and stubby fingers), distinctive facial structures (large tongue, flat profile, broad skull, slanting eyes, and round head), kidney defects, suppressed immune system, and malformations of the heart, ears, hands, and feet. Sexual maturity is rarely attained, and life expectancy is shorter.

Fertilization age Two weeks less than the gestational age, since a secondary oocyte is not fertilized until about 2 weeks after the last normal menstrual period.

Fetal alcohol syndrome (F.A.S) A specific pattern of fetal malformation due to intrauterine exposure to alcohol. F.A.S is one of the most common causes of mental retardation and the most common preventable cause of birth defects in the United States.

Gestational age (jes-TÃ-shun-al; gestatus = to bear) The age of an embryo or fetus calculated from the presumed first day of the last normal menstrual period.

Karyotype karyotip; karyo-= nucleus) The chromosomal characteristics of an individual presented as a systematic arrangement of pairs of metaphase chromosomes arrayed in descending order of size and according to the position of the centromere (see Figure 29.24); useful in judging whether chromosomes are normal in Klinefelter's syndrome An abn tion, usually due to trisomy Such individuals are somewhat with undeveloped testes, Lethal gene (Ló-thal Jón; lethum = death) A gene that, when expressed, results in death either in the embryonic state or shortly after birth.

Metafemale syndrome An abnormal sex chromosome configuration characterized by at least three X chromosomes (30) that occurs about once in every 700 births. These females have underdeveloped genital organs and limited fertility, and most are mentally retarded.

Primordium primordeum; primus-= first; -ordior = to begin) The beginning or first discernible indication of the development of an organ or structure.

Puerperal fever puerperal; puer = child) An infectious disease of childbirth, also called puerperal sepsis and childbed fever. The disease, which results from an infection originating in the birth canal, affects the mother's endometrium. It may spread to other pelvic structures and lead to septicemia.

Chapter Review

Review

29.1 Overview of Development

1. Pregnancy is a sequence of events that begins with fertilization, and proceeds to implantation, embryonic development, and fetal development. It normally ends in birth.

2. During the embryonic period (fertilization through the eighth week of development), the developing human is called an embryo.

3. During the fetal period (the ninth week of development until birth), the developing human is known as a fetus.

29.2 The First Two Weeks of the Embryonic Period

1. During fertilization a sperm penetrates a secondary oocyte and their pronuclei unite. Penetration of the zona pellucida is facilitated by enzymes in the sperm's acrosome. The resulting cell is a zygote.

2. Normally, only one sperm fertilizes a secondary oocyte because of the fast and slow blocks to polyspermy.

3. Early rapid cell division of zygote is called cleavage, and the cells produced by cleavage are called blastomeres. The solid sphere of cells produced by cleavage is a morula. The morula develops into a blastocyst, a hollow ball of cells differentiated into a tropoblast and an inner cell mass. The attachment of a blastocyst to the endometrium is termed implantation; it occurs as a result of enzymatic degradation of the endometrium. After implantation, the endometrium becomes modified and is known as the decidua. The trophoblast develops into the synctiotrophoblast and cytotrophoblast, both of which become part of the chorion. The inner cell mass differentiates into hypoblast and epiblast, the bilaminar (two-layered) embryonic disc.

4. The amnion is a thin protective membrane that develops from the cytotrophoblast.

5. The extraembryonic endoblast and hypoblast form the umbilical vesicle, which transfers nutrients to the embryo, forms blood cells, produces primordial germ cells, and forms part of the digestive canal.

6. Erosion of sinusoids and endometrial glands provides blood and secretions, which enter lacunar vascular circles to supply nutrition to and remove wastes from the embryo.

7. The extraembryonic coelom forms within extraembryonic mesoblast.

8. The extraembryonic mesoderm and trophoblast form the chorion, the principal embryonic part of the placenta.

Turner syndrome An abnormal sex chromosome configuration in females caused by the presence of a single X chromosome (designated X.O; occurring about once in every 5000 births, it produces a sterile female with virtually no ovaries and limited development of secondary sex characteristics. Other features include short stature, webbed neck, underdeveloped breasts, and widely spaced nipples. Intelligence usually is normal.

29.3 The Remaining Weeks of the Embryonic Period

1. The third week of development is characterized by gastrulation, the conversion of the bilaminar disc into a trilaminar (three-layered) embryo consisting of ectoderm, mesoderm, and endoderm. The first evidence of gastrulation is formation of the primitive streak, after which the primitive node, notochordal process, and notochord develop. The three primary germ layers form all tissues and organs of the developing organism. Table 29.1 summarizes the structures that develop from the primary germ layers. Also during the third week, the oropharyngeal and cloacal membranes form. The wall of the umbilical vesicle forms a small vascularized outpouching called the allantois, which functions in blood formation and development of the urinary bladder.

2. The process by which the neural plate, neural folds, and neural tube form is called neurulation. The brain and spinal cord develop from the neural tube.

3. Paraxial mesoderm segments to form somites from which skeletal muscles of the trunk and limbs develop. Somites also form the dermis, subcutaneous tissue, vertebrae, and ribs.

4. Blood vessel formation, called angiogenesis, begins in mesodermal cells called angioblasts.

5. The heart forms from mesodermal cells called the cardiogenic mesenchyme. By the end of the third week, the primitive heart beats and circulates blood. Chorionic villi, projections of the chorion, connect to the embryonic heart so that maternal and fetal blood vessels are brought into close proximity, allowing the exchange of nutrients and wastes between maternal and fetal blood.

6. Placentation refers to formation of the placenta, the site of exchange of nutrients and wastes between the mother and fetus. The placenta also functions as a protective barrier, stores nutrients, and produces several hormones to maintain pregnancy. The actual connection between the placenta and embryo (and later the fetus) is the umbilical cord.

7. Organogenesis refers to the formation of body organs and systems and occurs during the fourth week of development.

8. Conversion of the flat, two-dimensional trilaminar embryonic disc to a three-dimensional cylinder occurs by a process called embryonic folding. Embryonic folding brings various organs into their final adult positions and helps form the digestive canal.

9. Pharyngeal arches, grooves, and pouches give rise to the structures of the head and neck.

10. By the end of the fourth week, upper and lower limb buds develop, and by the end of the eighth week the embryo has clearly human features.

29.4 Fetal Period

1. The fetal period is primarily concerned with the growth and differentiation of tissues and organs that developed during the embryonic period.

2. The rate of body growth is remarkable, especially during the ninth and sixteenth weeks.

3. The principal changes associated with embryonic and fetal growth are summarized in Table 29.2.

29.5 Teratogens

1. Teratogens are agents that cause physical defects in developing embryos.

2. Among the more important teratogens are alcohol, pesticides, industrial chemicals, some prescription drugs, cocaine, L.S.D, nicotine, and ionizing radiation.

29.6 Prenatal Diagnostic Tests

1. Several prenatal diagnostic tests are used to detect genetic disorders and to assess fetal well-being. These include fetal ultrasonography, in which an image of a fetus is displayed on a screen; amniocentesis, the withdrawal and analysis of amniotic fluid and the fetal cells within it; and chorionic villi sampling, which involves withdrawal of chorionic villi tissue for chromosomal analysis.

2. Chorionic villi sampling can be done earlier than amniocentesis, and the results are available more quickly, but it is slightly riskier than amniocentesis.

3. Noninvasive prenatal tests include the maternal alpha-fetoprotein test to detect neural tube defects and the Quad A.F.P Plus test to detect Down syndrome, trisomy 18, and neural tube defects.

29.7 Maternal Changes During Pregnancy

1. Pregnancy is maintained by human chorionic gonadotropin, estrogens, and progesterone.

2. Human chorionic somatomammotropin contributes to breast development, protein anabolism, and catabolism of glucose and fatty acids.

3. Relaxin increases flexibility of the pubic symphysis and helps dilate the uterine cervix near the end of pregnancy.

4. Corticotropin-releasing hormone, produced by the placenta, is thought to establish the timing of birth, and stimulates the secretion of cortisol by the fetal suprarenal gland.

5. During pregnancy, several anatomical and physiological changes occur in the mother.

29.8 Exercise and Pregnancy

1. During pregnancy, some joints become less stable, and certain physical activities are more difficult to execute.

2. Moderate physical activity does not endanger the fetus in a normal pregnancy.

29.9 Labor

1. Labor is the process by which the fetus is expelled from the uterus through the vagina to the outside. True labor involves dilation of the cervix, expulsion of the fetus, and delivery of the placenta.

2. Oxytocin stimulates uterine contractions via a positive feedback cycle.

29.10 Adjustments of the Infant at Birth

1. The fetus depends on the mother for oxygen and nutrients, the removal of wastes, and protection.

2. Following birth, an infant's respiratory and cardiovascular systems undergo changes to enable them to become self-supporting during postnatal life.

29.11 The Physiology of Lactation

1. Lactation refers to the production and ejection of milk by the mammary glands.

2. Milk production is influenced by prolactin, estrogens, and progesterone.

3. Milk ejection is stimulated by oxytocin.

4. A few of the many benefits of breastfeeding include ideal nutrition for the infant, protection from disease, and decreased likelihood of developing allergies.

29.12 Inheritance

1. Inheritance is the passage of hereditary traits from one generation to the next.

2. The genetic makeup of an organism is called its genotype; the traits expressed are called its phenotype.

3. Dominant genes control a particular trait; expression of recessive genes is masked by dominant genes.

4. Many patterns of inheritance do not conform to the simple dominant-recessive patterns. In incomplete dominance, neither member of an allelic pair dominates; phenotypically, the heterozygote is intermediate between the homozygous dominant and the homozygous recessive. In multiple-allele inheritance, genes have more than two alternate forms. An example is the inheritance of A.B.O blood groups. In complex inheritance, a trait such as skin or eye color is controlled by the combined effects of two or more genes and may be influenced by environmental factors.

5. Each somatic cell has 46 chromosomes—22 pairs of autosomes and 1 pair of sex chromosomes.

6. In females, the sex chromosomes are two X chromosomes; in males, they are one X chromosome and a much smaller Y chromosome, which normally includes the prime male-determining gene, called S.R.Y.

7. If the S.R.Y gene is present and functional in a fertilized ovum, the fetus will develop testes and differentiate into a male. In the absence of S.R.Y, the fetus will develop ovaries and differentiate into a female.

8. Red-green color blindness and hemophilia result from recessive genes located on the X chromosome. These sex-linked traits occur primarily in males because of the absence of any counterbalancing dominant genes on the Y chromosome.

9. A mechanism termed X-chromosome inactivation (lyonization) balances the difference in number of X chromosomes between males (one 10) and females (two Xs). In each cell of a female's body, one X chromosome is randomly and permanently inactivated early in development and becomes a Barr body.

10. A given phenotype is the result of the interactions of genotype and the environment.

Critical Thinking Questions

1. Kathy is breastfeeding her infant and is experiencing what feel like early labor pains. What is causing these painful feelings? Is there a benefit to them?

2. Jack has hemophilia, which is a sex-linked blood-clotting disorder. He blames his father for passing on the gene for hemophilia. Explain to

Answers to Figure Questions

29.1 Capacitation is the group of functional changes in sperm that enable them to fertilize a secondary oocyte; the changes occur after the sperm have been deposited in the female genital tract.

29.2 A morula is a solid ball of cells; a blastocyst consists of a rim of cells (trophoblast) surrounding a cavity (blastocyst cavity) and an inner cell mass.

29.3 The blastocyst secretes digestive enzymes that eat away the endometrial lining at the site of implantation.

29.4 The basal decidua helps form the maternal part of the placenta.

29.5 Implantation occurs during the secretory phase of the uterine cycle.

29.6 The bilaminar embryonic disc is attached to the trophoblast by the connecting stalk.

29.7 Gastrulation converts a bilaminar embryonic disc into a trilaminar embryonic disc.

29.8 The notochord induces mesodermal cells to develop into vertebral bodies and forms the nucleus pulposus of intervertebral discs.

29.9 The neural tube forms the brain and spinal cord; somites develop into skeletal muscles of the trunks and limbs, subcutaneous tissue, dermis, vertebrae, and ribs.

29.10 Chorionic villi help to bring the fetal and maternal blood vessels into close proximity.

29.11 The placenta participates in the exchange of materials between fetus and mother, serves as a protective barrier against many microbes, and stores nutrients.

29.12 As a result of embryonic folding, the embryo curves into a C-shape, various organs are brought into their eventual adult positions, and the primitive gut is formed.

Jack why his reasoning is wrong. How can Jack have hemophilia if his parents do not?

3. Alisa has asked her obstetrician to save and freeze her baby's cord blood after delivery in case the child needs a future bone marrow transplant. What is in the baby's cord blood that could be used to treat future disorders in the child?

29.13 Pharyngeal arches, grooves, and pouches give rise to structures of the head and neck.

29.14 Fetal weight doubles between the midfetal period and birth.

29.15 Amniocentesis is used primarily to detect genetic disorders, but it also provides information concerning the maturity (and survivability) of the fetus.

29.16 Early pregnancy tests detect elevated levels of human chorionic gonadotropin.

29.17 Relaxin increases the flexibility of the pubic symphysis and helps dilate the cervix of the uterus to ease delivery.

29.18 Complete dilation of the cervix marks the onset of the stage of expulsion.

29.19 Oxytocin also stimulates contraction of the uterus during delivery of a baby.

29.20 The odds that a child will have P.K.U are the same for each child—25%.

29.21 In incomplete dominance, neither member of an allelic pair is dominant; the heterozygote has a phenotype intermediate between the homozygous dominant and the homozygous recessive phenotypes.

29.22 A baby can have blood type O if each parent is heterozygous and has one i allele.

29.23 Hair color, height, and body build are some of the traits passed on by complex inheritance.

29.24 The female sex chromosomes are X.X, and the male sex chromosomes are X.Y.

29.25 The chromosomes that are not sex chromosomes are called autosomes.

29.26 A red-green color-blind female has an X superscript c X superscript c genotype.

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