Hānau ka ʻāina, hānau ke aliʻi, hānau ke kanaka.

Born was the land, born were the chiefs, born were the common people.

The land, the chiefs, and the commoners belong together.

ʻŌlelo Noʻeau, compiled by Mary Kawena Pukui, #466

Introduction

Figure 28.1: Loʻi Kalo: In Hawaiian cosmogony, Hāloanakalaukapalili, the kalo, is the child of Wakea, sky father, and Hawaiian deity Hoʻohokukalani, and the older brother of the first Hawaiian human, Hāloa.

Development follows the growth pattern and differentiation of cells and tissue following fertilization. After an egg is fertilized by a sperm, a single cell, called a zygote, begins to divide. Thirty-eight weeks later, following many more divisions, that single cell will have developed into a baby. Development describes all the processes that occur during this process.

Gestation is a term used to describe a baby’s growth inside the mother’s uterus. The gestational calendar is usually 40 weeks, although gestation only lasts 38 weeks. This is because the gestational calendar begins on the first day of the mother’s last menstrual period (LMP), which is two weeks before ovulation occurs. The gestational period is often divided into three blocks called trimesters. Physiologically we can divide development into the embryonic period, the first eight weeks following fertilization, the fetal period, which extends from the end of the embryonic period to birth, and the postnatal period, which includes the first six weeks after birth.

This chapter will begin with a description of the process of development. It will then describe many of the changes that occur to the mother throughout gestation leading up to childbirth, followed by a description of some of the changes that occur to the newborn shortly after birth. The chapter ends with a brief description of genetics and patterns of inheritance.

28.1 Fertilization

Fertilization occurs when two gametes, an egg and a sperm, meet in the ampulla of the uterine (fallopian) tube and fuse to form a single cell called a zygote. The two gametes are haploid cells meaning they only have half of the usual genetic material. The zygote is a diploid cell with a complete set of chromosomes, half from the mother and half from the father. This section of the chapter will describe how the process of fertilization occurs.

Capacitation

Following ejaculation, hundreds of millions of sperm begin a seemingly impossible journey that maybe one will complete. The environment in the vagina is highly inhospitable to sperm due to the low pH (between 3.8-4.5). The acid kills millions of sperm, and many more are blocked by the cervical mucus plug that is normally an impenetrable barrier. However, around ovulation, the consistency of the mucus changes, and channels form, allowing some of the sperm to pass from the vagina into the uterus.

The small number of sperm that make it through the cervical os and into the uterus are aided in their journey by uterine contractions that move the sperm to the opening of the fallopian tube. However, of those that make it to the opening of a fallopian tube, only half will be at the correct tube since ovulation occurs in only one ovary each month. The few hundred sperm that finally reach the fallopian tube will be aided by peristaltic contractions, allowing some to reach the egg within an hour of ejaculation. However, these lucky few will not fertilize the egg. Before a sperm can fertilize an egg, it must undergo capacitation (priming). Capacitation takes about 10 hours. Fortunately, the fallopian tube is a much more hospitable environment than the vagina, and sperm can survive there for up to 5 days. During the process of capacitation, fluids within the female reproductive tract improve the movement of sperm and help to remove some of the cholesterol from the acrosome. This process is essential before sperm can undergo the acrosomal reaction process necessary to penetrate the barriers outside of the egg. The capacitation process, along with the survival time of the sperm, leads to a window of time during which sex can lead to a pregnancy. Since the egg is only viable for 24 hours after ovulation, the window of time that sex can result in a pregnancy is five days before ovulation and 14 hours after ovulation. After 14 hours, there will not be enough time for sperm to undergo capacitation. To determine when ovulation occurs, couples trying to conceive use methods such as monitoring basal body temperature, which goes up slightly, cervical mucus thickness, or they can monitor levels of luteinizing hormone in a home urine test. Some women can feel ovulation occur, and it can even be painful, a condition called mittelsmerz, German for middle pain since ovulation occurs at the midpoint of the menstrual cycle.

Sperm and Egg Fusion

After sperm has undergone capacitation, it is ready to fertilize an egg. This process begins when sperm reach the egg and undergo the acrosomal reaction in which the acrosomal enzymes hyaluronidase and acrosin are released (see figure). These enzymes help to digest a pathway through the corona radiata (granulosa cells) and the zona pellucida surrounding the egg, allowing the membrane of the sperm and egg to fuse. After the membranes fuse the pronucleus of the sperm is released into the egg. The nuclear membranes of the haploid pronuclei of the egg and the sperm can then fuse in a process called amphimixis. At this point fertilization is complete and the cell is now a diploid (2n) zygote with a complete set of genetic material.

Figure 28.3: Sperm and the Process of Fertilization (OpenStax)

Twins

If two eggs are released during ovulation, and both are fertilized, this leads to two separate zygotes and the development of dizygotic or fraternal twins. These twins are siblings born together and can be as similar or different as any brother or sister. However, if after fertilization of a single egg, a cell or cells split away from the developing embryo, two separate but genetically identical monozygotic or identical twins will develop.

Block to Polyspermy

After fertilization occurs, it is crucial to prevent any other sperm from fertilizing the same egg, a condition called polyspermy. Polyspermy would result in multiple copies of each chromosome such as triploidy (two sperm plus one egg or 3n) or tetraploidy (three sperm plus one egg or 4n) etc. Any more than two copies of each chromosome are not a survivable condition. This is different from having a third copy of a single chromosome in a condition called trisomy (2n + 1) which will be discussed later. Trisomy, unlike triploidy, is sometimes survivable and results in conditions such as trisomy 21 or Down syndrome. To prevent polyspermy, the zygote has some defense mechanism called the fast and slow block to polyspermy. In the fast block, the fusion of the sperm and egg plasma membranes causes sodium channels to open resulting in depolarization. This depolarization inhibits the fusion of any other sperm. In the slow block to polyspermy, the fusion of the sperm and egg causes calcium to enter triggering a cortical reaction. In the cortical reaction, a series of cortical granules, which are vesicles located just inside of the egg, fuse with the plasma membrane. The secretions from the cortical granules create an impenetrable barrier called the fertilization membrane.

28.2 Embryonic Development

After fertilization occurs, the conceptus, or early embryo, begins a series of rapid cell divisions called cleavage. The embryonic period lasts for 8 weeks and includes many important developmental processes including gastrulation and organogenesis. It is also during this period that the embryo implants into the endometrium of the mother’s uterus and the placenta begins to develop.

Cleavage and Hatching

After fertilization, the zygote begins to divide by undergoing mitosis. The resulting daughter cells are still contained within the fertilization membrane which cannot expand. Therefore, all the early cell divisions result in daughter cells half the parent cell’s size. This early stage of rapid cell division without the increase in the size of each cell is called cleavage, and the early cells are called blastomeres. The solid ball of cells that continues to move through the fallopian tube, is called a morula (Figure 28.5). By five days after fertilization, the morula reaches the uterus and begins to form a hollow space at its center. The conceptus is now called a blastocyst and the hollow space is called the blastocoel. The cells of the blastocyst can be divided into the cells that form the ball, called trophoblast cells, and a group of cells gathered at one pole called the inner cell mass or embryoblast. The trophoblast cells are important in the process of implanting in the uterus and will eventually form part of the placenta. The embryoblast will develop into the embryo. At this point, the blastocyst will break through the fertilization membrane in a process called hatching and on day six will begin to implant into the uterus.

Figure 28.5: Cleavage Stage and Hatching (OpenStax)

Implantation

On day six, after the blastocyst hatches, it contacts the endometrium, usually in the fundus region of the uterus (Figure 28.6). The trophoblast cells then begin to differentiate into two groups. An outer or superficial group of cells called syncytiotrophoblast, and an inner group of cells called the cytotrophoblast. The plasma membrane separating the cells of the syncytiotrophoblast breaks down forming a multinucleated cell mass, or syncytium. This syncytium begins to secrete lytic enzymes allowing it to burrow into the endometrium like roots (Figure in the Development of Membrane section- two figures down). The cells of the cytotrophoblast grow into the path digested by the syncytiotrophoblast, forming bumps or villi. Later in development, the cytotrophoblast will associate with a layer of cells called extraembryonic mesoderm and will change its name from cytotrophoblast to chorion, and the bumps will be the chorionic villi. These chorionic villi will eventually grow and branch extensively forming the embryonic or fetal portion of the placenta. The implantation process takes about a week, and by the end, the conceptus is completely buried and covered by the endometrium.

Another role of the trophoblast is the secretion of hormones. One of these hormones is called human chorionic gonadotropin (hCG). hCG, which is the hormone detected in pregnancy tests, feeds back to maintain the corpus luteum in the ovary. Without progesterone from the corpus luteum, the endometrium, along with the embryo, will be shed in menstruation. Therefore, the trophoblast is critical in maintaining the pregnancy in the early stages. Later in pregnancy, the placenta takes overproduction of progesterone and estrogen and the corpus luteum is no longer necessary.

Figure 28.6: Implantation (OpenStax)

Development of Membranes

After implantation, the conceptus begins to develop into an embryo, a process called embryogenesis. This begins with the differentiation of the embryoblast into a two-layered structure called the embryonic disc (Figure 28.7). These layers are called the hypoblast (later the endoderm) and the epiblast (later the ectoderm). The cells of the hypoblast divide to form a cavity called the yolk sac. The yolk sac is the site of early blood cell production. It is also the location of the germ cells that will later migrate to the gonads and become spermatogonia or oogonia. The cells of the epiblast also form a space. The amniotic membrane encloses this space called the amniotic cavity filled with amniotic fluid. This is the liquid-filled space in which the embryo and fetus will develop. The function of the amniotic fluid is to protect the growing fetus from trauma, infection, and temperature variation. It also allows the fetus freedom of movement and prevents adhesions from forming between the fetus and mother. Amniotic fluid thus plays an important role and low levels, a condition called oligohydramnios, can cause serious problems.

Another membranous structure that forms is called the allantois, which begins as an out pocket near the yolk sac. The allantois forms the basis for the development of the umbilical cord and forms part of the urinary bladder.

The chorion membrane was described earlier. It forms from the cytotrophoblast after the extraembryonic mesoderm covers it. As the amniotic membrane and cavity expand it eventually extends to the chorion and we then call it the amniochorionic membrane. It is this structure along with the thin covering of the endometrium that the fetus must break through when the “membranes” are ruptured during childbirth.

Development of the Embryonic Disc (OpenStax)

Fetal Membranes: Includes the allantois and the amniochorionic membrane (Wiki)

Figure 28.7: Embryonic Disc and Fetal Membranes

Gastrulation

On day 15, a thickened region called the primitive streak forms in the midline of the epiblast (Figure 28.8). The primitive streak forms a groove through which the dividing cells of the epiblast migrate forming a third layer called the mesoderm. In addition, these migrating cells replace the hypoblast to form the endoderm. The cells of the epiblast become the ectoderm. This process of forming a three-layered disc is referred to as gastrulation and it is technically the beginning of the embryonic period and the beginning of organogenesis. Once the three primary germ layers (endoderm, mesoderm, and ectoderm) are present, each of these germ layers can develop into specific structures in the human body allowing organ formation to begin. Although most of the mesodermal cells remain sandwiched between the ectoderm and the endoderm, some of them migrate beyond the embryonic disc to form the extraembryonic mesoderm. As mentioned earlier, this is when the trophoblast becomes the chorion.

Figure 28.8: Gastrulation and Formation of the Primary Germ Layers (OpenStax)

Organogenesis

The cells of the primary germ layers continue to grow and differentiate to form tissues, and organs (Figure 28.9). The endoderm forms the epithelial lining of the gastrointestinal and respiratory tracts. It also forms the organs and glands that develop from the invagination of this epithelium including the liver and the pancreas. The ectoderm forms the epithelial covering of the body, the epidermis, along with the structures that develop from it, such as hair and nails. The ectoderm also forms the nervous system. While the cells of the endoderm and the ectoderm remain attached to form epithelial sheets or solid organs, the mesoderm develops into a loose tissue called mesenchyme. This mesenchyme will differentiate into muscle and all the connective tissues of the body including bone. Some mesenchymal cells remain attached to form the inner lining of blood vessels (endothelium) and the serosal membranes (mesothelium) of the peritoneal, pleural and pericardial cavities. Additionally, the extraembryonic mesoderm will form the blood vessels outside of the fetus, including the blood vessels of the umbilical cord and placenta.

Figure 28.9: Fates of the Germ Layers in the Embryo (OpenStax)

The formation of the nervous system from the ectoderm occurs during the process of neurulation (Figure 28.10). Neurulation begins with the development of the notochord from the mesoderm just below the ectoderm. The notochord begins the differentiation of the ectoderm above it into the neural plate. Eventually, the notochord becomes the nucleus pulposus of the intervertebral discs. The neural plate begins to fold in closing off to form a neural tube. This closure begins in the middle and proceeds forward and backward. The closure of the neural tube is sometimes incomplete. When the tube does not close towards the rostral end, it causes the condition known as anencephaly (“without a brain”) which is always fatal although babies sometimes live for a few minutes due to the presence of the hindbrain which controls the heart and lungs. When the tube does not close caudally, it causes a condition called spina bifida which ranges in severity from a hidden or occult form to more severe forms that cause paralysis of the lower extremities. The closure of the neural tube is dependent on folic acid which is why women that may become pregnant should make sure to get that vitamin in their diets or from prenatal supplements. The neural tube forms the central nervous system including the brain and the spinal cord. The cells of the neural plate just outside of the neural tube are called neural crest cells and they form components of the peripheral nervous system.

Figure 28.10: Neurulation (OpenStax)

As the layers and organs begin to develop, there are several folds of the embryo that must occur (Figure 28.11). The endoderm folds over on itself to form a tube which will become the alimentary canal of the digestive system. The ectoderm and the amniotic sac fold-over rostrally, caudally, and laterally to surround and completely enclose other structures of the developing embryo so that it is enclosed in an outer covering that becomes the epidermis and so that the entire embryo is now enclosed within the amniotic cavity. Meanwhile, the mesoderm forms into balls of mesenchyme called somites forming segments along the long axis of the body. As the somites grow and surround other structures they split into two layers forming true internal cavities, or coeloms, between the layers. In this way, the peritoneal cavity, the pleural cavity, and the pericardial cavities develop. The two layers become the parietal and visceral serosae that line the cavities and cover the organs found within those cavities.

Figure 28.11: Embryonic Folding (OpenStax)

28.3 The Placenta

The developing embryo and fetus are entirely dependent on the mother. The fetus does not eat, does not breathe, and does not have fully functional kidneys for the elimination of waste. Therefore, the development of the placenta, which performs all these tasks, is critical for development.

Placentation

As illustrated in the previous figures (Figures from Membranes and Germ Layers), the trophoblast differentiates into the syncytiotrophoblast and the cytotrophoblast. After implantation, maternal blood vessels invade this space and fill the space with blood. The chorionic villi composed of cytotrophoblast continue to grow and branch and are invaded by embryonic capillaries that develop from the extraembryonic mesoderm. These chorionic villi are bathed in maternal blood that fills the intervillous space (Figure 28.12). As the villi grow and increase, their surface area, the outer covering of the cytotrophoblast becomes a single layer of cells. This arrangement is remarkably similar to the respiratory membrane in the lungs with two cell layers separated by a basement membrane. This is also similar to the arrangement in the filtration membrane of the kidney and the membrane through which nutrients are absorbed in the small intestine. The great surface area of the lungs, the small intestine, and the kidney tubules are also similar to the surface area of the placenta. As the placenta develops and grows, the branching and thinning of the layers results in increasing placental conductivity, allowing greater levels of exchange of gasses, nutrients, and waste between embryonic and maternal circulation. Although the placenta begins functioning less than four weeks after fertilization, it is not able to supply all the fetal nutrition until around the 12th week. Before that the conceptus receives early nutrition from the glycogen-rich fluids secreted by the fallopian tubes and endometrial glands. During and after implantation, the embryo receives many of its nutrients from trophoblastic nutrition which comes from the digestion of endometrial cells by the trophoblast.

Figure 28.12: Cross Section of the Placenta (OpenStax)

Placental Pathology

As mentioned above, the placenta usually develops in the fundus of the uterus. However, in approximately four in 1000 births, the placenta completely or partially covers the internal os or opening of the cervix. This is an extremely dangerous condition known as placenta previa (Figure 28.13). Because the placenta is so highly vascular, placenta previa was once a common cause of fetal and maternal mortality. Now that C-sections have become routine, placenta previa is a manageable condition. Mothers will be aware of the condition if they are receiving adequate prenatal care and their doctor will schedule a C-section. However, the condition can still cause bleeding and is a common cause of bright red and painless vaginal bleeding in the second half of pregnancy.

Figure 28.13 Placenta Previa An embryo that implants too close to the opening of the cervix can lead to placenta previa, a condition in which the placenta partially or completely covers the cervix. (From OpenStax)

Another common problem that can develop is placental abruption. Placental abruption is a partial or complete separation of the placenta from the endometrium. Symptoms include vaginal bleeding and abdominal pain most often in the third trimester. The extent of the symptoms and the medical management of this condition depends on the extent of the separation. The most minor abruption may have no symptoms at all and the mother may be unaware. For this reason, any trauma, which is the most common cause of placental abruption, should be followed up with treatment including imaging and administration of Rho-GAM. Because placental abruption will cause comingling of maternal and fetal blood it will be necessary for the mother to get a Rho-GAM injection to prevent her immune system from becoming sensitized to the Rh antigen if the mother is Rh-negative.

Placental Conduction

As described above the placenta is the most vital source of fetal nutrition. However, there are substances other than nutrients that cross between fetal and maternal circulation. Different substances cross using diffusion (oxygen and carbon dioxide), facilitated diffusion (glucose), active transport (amino acids), and receptor-mediated endocytosis (maternal IgG antibodies). Some substances can cross to cause illness or birth defects. These include drugs such as alcohol, nicotine, opioids, and benzodiazepines. Some microorganisms can cross, including the TORCH agents, a mnemonic term to help you remember Toxoplasmosis, Other agents, Rubella, Cytomegalovirus, and Herpes simplex. The result of these infections depends on the organism and when during pregnancy it is contracted and can range from minor to severe.

Many substances do not cross the placenta, including most bacteria and fungi. Additionally, blood cells do not cross. As mentioned earlier, this is important to prevent the immune sensitization of the mother to fetal antigens. It is also essential to prevent maternal T lymphocytes from crossing and destroying the fetus due to all the “non-self” antigens displayed by its cells.

28.4 Fetal Development

The embryonic period is completed at the end of the eighth week. From the ninth week until birth is considered to be the fetal period. Most of the major organ development occurs during the embryonic period. Most organ growth and maturation occurs after this stage.

Sexual Differentiation

Unlike most organ development, sexual differentiation does not occur until the fetal period during the 9th-12th week. Until this time the cloaca (opening for the digestive, reproductive and urinary system) and bipotential gonads (able to develop into male or female gonads) have not developed. In addition, two sets of duct systems give the potential for the development of either morphological gender. The natural course of development is female. Without something interfering with this process a fetus will always develop as a female.

In the process of female development, one of the two duct systems, the Wolffian ducts (also known as mesonephric ducts) degenerate and the Mullerian ducts (also known as paramesonephric ducts) develop into the fallopian tubes and uterus (Figure 28.14). The bipotential gonads develop into ovaries and the external genitalia develops as female with the cloaca becoming the urethra and rectum.

If, on the other hand, the fetus has a Y chromosome, they produce a protein from the sex-determining region of the Y (SRY) gene on the Y chromosome, which causes the bipotential gonads to develop as testes and epididymis. The SRY protein also causes anti-Mullerian hormone (AMH) to be produced resulting in the development of the Wolffian ducts into the vas deferens and the degeneration of the Mullerian ducts (Figure 28.14). The testes, in turn, produce testosterone which causes the external genitalia to develop as male with the cloaca becoming the urethra and rectum.

Figure 28.14: Sexual Differentiation (OpenStax)

Fetal Circulation

During prenatal development, the fetal circulatory system is integrated with the placenta via the umbilical cord so that the fetus receives both oxygen and nutrients from the placenta. However, after childbirth, the umbilical cord is severed, and the newborn’s circulatory system must be reconfigured. When the heart first forms in the embryo, it exists as two parallel tubes derived from mesoderm and lined with endothelium, which then fuses together. As the embryo develops into a fetus, the tube-shaped heart folds and further differentiates into the four chambers present in a mature heart. Unlike a mature cardiovascular system, however, the fetal cardiovascular system also includes circulatory shortcuts, or shunts. A shunt is an anatomical (or sometimes surgical) diversion that allows blood flow to bypass immature organs such as the lungs and liver until childbirth.

The placenta provides the fetus with necessary oxygen and nutrients via the umbilical vein. (Remember that veins carry blood toward the heart-in this case, toward the fetal heart). The blood flowing through the umbilical vein is oxygenated because it comes from the placenta. The respiratory system is immature and cannot yet oxygenate blood on its own and there is no air for the fetus to breathe. Thus, the pulmonary vein does not carry oxygenated blood to the heart until after birth. From the umbilical vein, the oxygenated blood flows toward the inferior vena cava, all but bypassing the immature liver, via the ductus venosus shunt (Figure 28.15). The liver receives just a trickle of blood, which is all that it needs in its immature, semi-functional state. Blood flows from the inferior vena cava to the right atrium, mixing with fetal venous blood along the way.

Although the fetal liver is semi-functional, the fetal lungs are nonfunctional. The fetal circulation, therefore, bypasses the lungs by shifting some of the blood through the foramen ovale, a shunt in the atrial septum that directly connects the right and left atria and avoids the pulmonary trunk altogether (Figure). Most of the rest of the blood is pumped to the right ventricle, and from there, into the pulmonary trunk, which splits into pulmonary arteries. However, a shunt within the pulmonary artery, the ductus arteriosus, diverts a portion of this blood into the aorta (Figure). This ensures that only a small volume of oxygenated blood passes through the immature pulmonary circuit, which has only minor metabolic requirements. Blood vessels of uninflated lungs have high resistance to flow, a condition that encourages blood to flow through the ductus arteriosus into the aorta, which presents much lower resistance. The oxygenated blood moves through the foramen ovale into the left atrium, where it mixes with the now deoxygenated blood returning from the pulmonary circuit. This blood then moves into the left ventricle, where it is pumped into the aorta. Some of this blood moves through the coronary arteries into the myocardium and some moves through the carotid arteries to the brain.

The descending aorta carries partially oxygenated and partially deoxygenated blood into the lower regions of the body. It eventually passes into the umbilical arteries through branches of the internal iliac arteries (Figure 28.15). The deoxygenated blood collects waste as it circulates through the fetal body and returns to the umbilical cord. Thus, the two umbilical arteries carry blood low in oxygen and high in carbon dioxide and fetal wastes. This blood is filtered through the placenta, where wastes diffuse into the maternal circulation. Oxygen and nutrients from the mother diffuse from the placenta into the fetal blood, and the process repeats.

Figure 28.15: Fetal Circulatory System (OpenStax)

Development of Other Organ Systems

From 9-12 weeks, the central nervous system continues to expand, the body elongates, and ossification continues. The bone marrow begins the process of erythrocyte production, along with the liver and spleen, and the liver starts to secrete bile. The fetus circulates amniotic fluid by swallowing it and producing urine. The fingers and toes begin to develop nails. By week 12, the eyes are well-developed. At the end of week 12, the fetus is about three inches long and weighs about 28 grams.

Weeks 13-16 are marked by sensory organ development. The eyes move closer together, and the ears move upward and lie flatter against the head. The kidneys are well-formed, and meconium, or fetal feces, consisting of ingested amniotic fluid, cellular debris, mucus, and bile, begins to accumulate in the intestines. At 16 weeks, the fetus is approximately 4.5 inches long and fingers and toes are fully developed.

During weeks 16-20, the limb movements become more powerful and the mother may begin to feel quickening or fetal movements. The sebaceous glands coat the skin with a waxy, protective substance called vernix caseosa that protects and moisturizes the skin and provides lubrication during childbirth. A silky hair called lanugo also covers the skin, but it is shed as the fetus continues to grow.

During weeks 21-30, the fetus gains weight rapidly by laying down fat. The bone marrow completely takes over erythrocyte synthesis, and the axons begin to be myelinated. The eyes can be opened and closed. The lungs begin to produce surfactant which reduces tension in the lungs and assists lung expansion after birth. In male fetuses, the testes descend into the scrotum toward the end of this period. The internal organs such as the lungs, heart, stomach, and intestines have formed enough by the end of this period that a fetus born prematurely at this point has a chance to survive outside of the mother’s womb if given intensive care. At 30 weeks, the fetus measures 11 inches.

From week 31 until birth, the fetus continues to lay down subcutaneous fat. At 36 weeks, the fetus is almost ready for birth. By week 37, all the organ systems are developed enough that the fetus could survive outside the mother’s uterus without many of the risks associated with premature birth.

Organs are vulnerable to damage at specific points during development (Figure 28.16). They are most susceptible to major damage as they are being formed initially during organogenesis during the embryonic period. However, certain organs, such as the CNS, remain susceptible to damage for much longer periods since major development continues through much of the fetal period. This has led to the concept of critical windows which are the specific ranges during which each organ or part of the body is susceptible to harmful substances such as teratogens or radiation. The concept is well illustrated by the drug thalidomide which was given to pregnant women to treat morning sickness during the 1960s. It later became clear that the drug could cause major birth defects but only if taken during the critical window of limb development. Many women who took this drug between 20 and 36 days after fertilization had babies born with short and malformed or completely lacking limbs. Drugs are now classified based on risk to developing babies. Thalidomide would have received an “X” classification if it had been thoroughly tested as is required today.

Figure 28.16 Critical Periods of Prenatal Development This image summarizes the three developmental periods in prenatal development. The blue images indicate where major development is happening and the aqua indicates where refinement is happening. As shown, most organs are particularly susceptible during the embryonic period. The central nervous system continues to develop in major ways through the fetal period as well. (Lumen)

28.5 Maternal Changes: Pregnancy, Labor, and Childbirth (Delivery)

Changes during Pregnancy

Pregnancy Hormones

Virtually all the effects of pregnancy can be attributed in some way to the influence of hormones. During the first 12 weeks of pregnancy, the corpus luteum in the ovary generates the pregnancy hormones. Progesterone and estrogens maintain the endometrial lining of the uterus. During weeks 12 -17, the placenta gradually takes over as the endocrine organ of pregnancy and provides high levels of progesterone and estrogens. Progesterone maintains the endometrial lining of the uterus to allow successful implantation and maintain the pregnancy by inhibiting uterine contractions. It also causes mammary glands to develop. Estrogen levels increase throughout the pregnancy, resulting in a 30-fold increase by childbirth. In addition to promoting the growth of fetal tissues, estrogens prevent ovulation by suppressing FSH and LH production and stimulating the enlargement of the uterus and proliferation of ducts in the mammary glands. The human chorionic gonadotropin (hCG) secreted by the trophoblast causes the corpus luteum to survive and continue producing progesterone and estrogens. By the eighth day after fertilization, hCG can be detected in the blood and urine of the mother, and the level peaks around 9-weeks. In addition to maintaining the corpus luteum, hCG also stimulates the male fetal gonads to secrete testosterone for the development of the male reproductive system. The levels of hCG decrease sharply near the end of the third month. Relaxin is another hormone secreted by the corpus luteum and then by the placenta. Relaxin increases the elasticity of the pubic symphysis and pelvic ligaments allowing expansion of the pelvis for the growing fetus and helping dilate the cervix during labor. Human chorionic somatomammotropin (hCS), also known as human placental lactogen (hPL), is another hormone produced by the placenta and plays a role in preparing the breasts for lactation. The anterior pituitary enlarges and ramps up the production of thyrotropin (increases the thyroid hormone and raises the maternal metabolic rate), prolactin (enlargement of mammary glands), and adrenocorticotropic hormone (ACTH: increases cortisol secretion which contributes to fetal protein synthesis) during pregnancy. In addition, parathyroid hormone levels increase and calcium is mobilized from the maternal bones for fetal use.

The second and third trimesters of pregnancy are associated with dramatic maternal anatomy and physiology changes. The most visible anatomical sign of pregnancy is the enlargement of the abdominal region, coupled with maternal weight gain. The weight gain is the result of the growing fetus as well as the enlarged uterus, amniotic fluid, placenta, breast tissue, and increased blood volume. During the second and third trimesters, the mother’s appetite increases to support this growth.

As the woman’s body adapts to pregnancy, pregnancy-induced physiologic changes occur in many organ systems.

Changes in Circulatory System

Blood volume increases by 30 percent of the preconception volume to manage the demands of the fetus for nutrients and oxygen, and waste removal. The blood pressure and pulse rise in conjunction with increased blood volume. As the fetus grows, the uterus compresses underlying pelvic blood vessels, hampering venous return from the legs and pelvic region. As a result, many pregnant women develop edema in the lower limbs and varicose veins or hemorrhoids.

Changes in Respiratory System

To meet the growing oxygen demands of the fetus and increased maternal metabolism, a pulmonary function also changes during pregnancy, especially during the second half of the pregnancy. The respiratory minute volume (volume of gas inhaled or exhaled by the lungs per minute) increases significantly. Dyspnea (difficulty breathing) also occurs because the growing uterus occupies most of the pelvic and abdominal cavities, exerting pressure against the diaphragm toward the end of the pregnancy. During the last several weeks of pregnancy, the pelvis becomes more elastic, and the fetus descends lower in a process called lightening. This typically ameliorates the dyspnea by taking the pressure off the diaphragm.

Changes in Integumentary System

The dermis stretches extensively to accommodate the growing uterus, breast tissue, and fat deposits. Torn connective tissue beneath the dermis can cause striae (stretch marks) over the abdomen, which appear as red or purple marks during pregnancy that fade to a silvery-white color in the months after childbirth. An increase in the melanocyte-stimulating hormone, in conjunction with estrogens, darkens the areolae of the breast and creates a dark line from the umbilicus to the pubis called the linea nigra (Figure 28.17). Melanin production during pregnancy may also darken or discolor skin around the eyes and cheekbones to create a chloasma, or “mask of pregnancy.”

Figure 28.17: Linea Nigra (OpenStax). The linea nigra, a dark medial line running from the umbilicus to the pubis, forms during pregnancy and persists for a few weeks following childbirth. The linea nigra shown here corresponds to a pregnancy that is 22 weeks along.

Changes in Digestive and Urinary Systems

A common gastrointestinal complaint during the later stages of pregnancy is gastric reflux, or heartburn, which results from the upward, constrictive pressure of the growing uterus on the stomach. The same decreased peristalsis that may contribute to nausea in early pregnancy is also thought to be responsible for pregnancy-related constipation as pregnancy progresses. The downward pressure of the uterus also compresses the urinary bladder, leading to frequent urination. The problem is exacerbated by increased urine production. Because of the increased maternal blood volume and blood pressure, the renal plasma flow and glomerular filtration rate increase. In addition, the maternal urinary system processes both maternal and fetal wastes, further increasing the total volume of urine.

Food and Environment

Food for wahine hāpai

Traditionally Hawaiians have taken great care of the expecting mothers. As their bodies swelled, family members rub kukui nut oil on their skin. In about the fourth month of pregnancy, they are put on a fairly high-vitamin and roughage, low-fat diet. Salty food and starch and fatty foods are avoided. They are supposed to eat a lot of greens; pōpolo, ‘āheahea, lu’au (taro leaves), palula (cooked sweet potato leaves). After the sixth month, they are not to eat too much to avoid giving birth to a large baby. And from the last two months until birth, they are given ‘ilima blossoms or hau blossoms every day which are supposed to act as lubricants to “slide” the baby out easily. These traditional practices match what western medicine is finding out. Avoid a lot of salt, starch, and fat, and eat more whole grains and plants (which are rich in vitamins and fibers) and seafood. They have been ahead of their time and known how to take care of their wahine hāpai (pregnant women) and keiki using the natural resources available to them. By the way, they have also believed that the food cravings are the craving of the baby within the pregnant women and not her own cravings. Now you can blame those strange food cravings on your unborn baby!

Hau Blossoms (Wiki)	ʻIlima (Wiki)	ʻĀheahea (Wiki)

Figure 28.18: Traditional ʻŌiwi pregnancy foods

https://ulukau.org/elib/cgi-bin/library?e=d-0qlcc2-000Sec–11haw-50-20-frameset-boo–1-010escapewin&a=d&d=D0.3.1&toc=0

Changes during Childbirth

Labor is the process by which the fetus is expelled from the uterus through the vagina. Childbirth, or parturition, typically occurs within a week of a woman’s due date. As pregnancy progresses into its final weeks, several physiological changes occur in response to hormones that trigger labor. Recall that progesterone inhibits uterine contractions. As the pregnancy nears the end, the progesterone levels start to drop and the estrogen levels continue to increase. The increasing ratio of estrogen to progesterone makes the myometrium of the uterus more sensitive to stimuli that promote contractions. In addition, the fetus starts to secrete cortisol which boosts the estrogen secretion by the placenta. Some women may experience weak and irregular Braxton Hicks contractions, also called false labor, because of decreasing levels of progesterone in late pregnancy.

Increased estrogen levels cause the myometrium to increase its sensitivity to oxytocin, a hormone that stimulates the contractions of labor. Meanwhile, the posterior pituitary has been boosting its secretion of oxytocin. As labor nears, oxytocin begins to stimulate stronger, more painful uterine contractions, in a positive feedback loop. Relaxin from the placenta increases the flexibility of the pubic symphysis and helps dilate the cervix. In addition, prostaglandins released from the placenta also enhance the uterine contraction strength and help soften the cervix. When a pregnancy is not progressing to labor and needs to be induced, a pharmaceutical version of oxytocin called pitocin is administered by intravenous drip to stimulate contractions and misoprostol, a synthetic prostaglandin analogue, is applied to the cervix to stimulate dilation.

Stretching of the myometrium and cervix by a full-term fetus in the vertex (head-down) position is regarded as a stimulant to uterine contractions. The contractions during parturition are under the positive feedback loop (Figure below). Cervical stretching induces uterine contraction, dilation of the cervix, and release of oxytocin that triggers more powerful contractions. These changes initiate the regular contractions known as true labor, which become more powerful and more frequent with time.

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Figure 28.19 Positive Feedback Loop of Childbirth. (Openstax) Normal childbirth is driven by a positive feedback loop.

Stages of Childbirth

The process of childbirth is divided into three stages: cervical dilation, the expulsion of the newborn, and afterbirth (Figure 28.20).

Figure 28.20 Stages of Childbirth. (from Openstax) The stages of childbirth include Stage 1, early cervical dilation; Stage 2, full dilation and expulsion of the newborn; and Stage 3, delivery of the placenta and associated fetal membranes. (The position of the newborn’s shoulder is described relative to the mother.)

The time of onset of labor to the complete dilation of the cervix is the stage of dilation. The cervix must dilate fully to 10 cm in diameter- wide enough to deliver the newborn’s head. This stage typically takes 6-12 hours, but it varies widely from minutes to days typically becoming much shorter after the first pregnancy. When labor begins, uterine contractions may occur only every 3–30 minutes and last only 20–40 seconds; however, by the end of this stage, contractions may occur as frequently as every 1.5–2 minutes and last for a full minute. The amniotic membranes rupture before the onset of labor in about 12 percent of women; they typically rupture at the end of the dilation stage in response to excessive pressure from the fetal head entering the birth canal.

Each contraction sharply reduces oxygenated blood flow to the fetus. For this reason, a period of relaxation must occur after each contraction to restore the oxygenated blood flow to the fetus. Fetal heart rate is monitored during childbirth to detect any abnormal changes. When blood flow to the fetus is blocked for a prolonged period or the head is compressed as a result of too forceful or lengthy contractions it can indicate fetal distress. In such a situation, an emergency cesarean section (C-section) may be necessary (See Clinical Application about C-section below).

The expulsion stage begins when the fetal head enters the birth canal and ends with the birth of the newborn. It could take from 10 minutes to several hours, depending in part on the orientation of the fetus. The vertex presentation is the most common and is associated with the greatest ease of vaginal birth. The fetus faces the maternal spinal cord and the smallest part of the head (the posterior aspect called the occiput) exits the birth canal first. In fewer than 5 percent of births, the infant is oriented in the breech presentation where the fetal buttocks or lower limbs enter the birth canal first. Today, most breech births are delivered surgically by caesarian section (See Clinical Application).

The delivery of the placenta and associated membranes, commonly referred to as the afterbirth, is the final stage of childbirth. After the expulsion stage, the myometrium continues to contract, detaching the placenta from the uterine wall and delivering through the vagina. The placenta is typically delivered within 30 minutes of the baby, but it can happen much faster if the abdomen is massaged. Continued contraction of the uterus also constricts blood vessels and reduces blood loss from the site of the placenta.

Delivery of the placenta marks the beginning of the postpartum period- the period approximately six weeks immediately following childbirth. During this period, the mother’s body gradually returns to a non-pregnant state.

The uterine contraction continues for several hours after birth and the uterus returns to its pre-pregnancy size in a process called involution. Mothers also experience a postpartum vaginal discharge called lochia, which is made up of uterine lining and blood initially, and later serous fluid.

Lactation

Lactation is the secretion and ejection of milk from the mammary glands. The mammary gland is composed of milk-transporting lactiferous ducts and milk-producing alveoli. These structures expand and increase in numbers during pregnancy in response to the various pregnancy-associated hormones. Prolactin is the main hormone that promotes milk production and secretion. The level of prolactin increases during pregnancy and eventually reaches 10-20 times the pre-pregnancy level, but the estrogen and progesterone from the placenta inhibit the milk secretion during pregnancy. Only when the placenta is expelled is this inhibition lifted and milk secretion begins.

When the infant suckles, suckling triggers nerve impulses in the areola of the breast that are relayed to the hypothalamus. In response, oxytocin is secreted from the hypothalamus and posterior pituitary. Oxytocin stimulates the contraction of alveoli and ducts and the milk drains into the mammary ducts and is suckled by the infant. This process is called the milk-let down reflex, and it is a positive feedback loop (Figure below). Stimuli other than suckling, such as hearing a baby’s cry can also trigger this reflex.

Figure 28.21 Milk Let-Down Reflex. (From OpenStax) A positive feedback loop ensures continued milk production as long as the infant continues to breastfeed.

In the final weeks of pregnancy and the first few days after birth, the mammary glands produce a thick, yellowish fluid called colostrum. Compared to regular breast milk, colostrum is high in proteins but contains less fat and glucose. It is rich with immunoglobulins and confers immunity to protect the newborn after the first few days of birth.

After the third postpartum day, the colostrum transitions to mature milk, which also contains immunoglobulins and other substances and nutrients that are ideal for the baby’s body needs and digestion. Breastfeeding also transfers the maternal microbiome and transfers beneficial bacteria to the baby’s gut. A mother can continue to lactate for years, but once breastfeeding is stopped, the milk production will stop. Lactation often blocks ovarian cycles for several months by decreasing the LH and FSH levels. However, it is a common misconception that you cannot get pregnant while nursing, and many women do conceive while breastfeeding.

28.6 Adjustments of the Infant at Birth and Postnatal Stages

At birth, the fetus experiences a dramatic transition of the environment; floating in the warm amniotic fluid inside the womb and continuously supplied with nutrients and oxygen from the placenta to a cold world where they experience hunger and thirst and use their lungs to breathe. The neonatal period spans the first to the thirtieth day of life outside of the uterus where the newborn’s body makes dramatic adjustments to the new environment.

Respiratory Adjustment

The fetal lungs are collapsed and filled with amniotic fluid because the placenta supplies the fetus with all the oxygenated blood it needs and the lungs are not used. After delivery, oxygenated blood flow from the placenta to the fetus is reduced and the carbon dioxide levels in the blood build-up. The high carbon dioxide levels in the blood stimulate the respiratory center in the brainstem, triggering the newborn to contract the respiratory muscles and take a big breath. The first breath inflates the collapsed lungs to nearly full capacity. After the lungs inflate, the baby exhales vigorously and produces the first cry. The dramatic decrease in the lung pressure and resistance to blood flow in the expanded lungs cause a major adjustment in circulation. Blood starts to flow into the pulmonary capillaries and red blood cells begin exchanging carbon dioxide for oxygen with air in the alveoli.

Circulatory Adjustment

The newborn’s first breath is vital to initiate the transition from the fetal to the neonatal circulatory pattern. Inflation of the lungs decreases blood pressure throughout the pulmonary system, as well as in the right atrium and ventricle. In response to this pressure change, the flow of blood temporarily reverses direction through the foramen ovale, moving from the left to the right atrium, and blocking the shunt with two flaps of tissue (Figure below). Within 1 year, the tissue flaps usually fuse over the shunt, turning the foramen ovale into a shallow depression called the fossa ovalis. However, sometimes a hole remains in the atrial septum in a condition called patent foramen ovale (PFO).

The ductus arteriosus constricts because of increased oxygen concentration (Figure below). Closing of the ductus arteriosus ensures that all blood leaving the right ventricle will travel to the lungs via the pulmonary arteries and become oxygenated by the newly functional neonatal lungs. The closed ductus arteriosus eventually becomes the ligamentum arteriosum. The ductus arteriosus generally does not completely close for several months after birth. Patent ductus arteriosus is a prolonged incomplete closure of the ductus arteriosus.

The process of clamping and cutting the umbilical cord collapses the umbilical blood vessels. The collapsed vessels atrophy and become ligaments of the abdominal wall and liver such as umbilical ligaments and round ligaments of the liver. The ductus venosus, which brought oxygenated blood from the umbilical vein to the inferior vena cava, degenerates to become the ligamentum venosum beneath the liver (Figure below). Now, the inferior vena cava only receives deoxygenated blood and brings it to the right atrium.

Figure 28.22: Circulatory Adjustments in Newborn. (From Openstax) A newborn’s circulatory system reconfigures immediately after birth. Ductus arteriosus constricts and foramen ovale closes in the heart. The umbilical vein stops delivering blood from the placenta and ductus venosus closes permanently.

Other Adjustments

At birth, the fetus transitions from floating in warm amniotic fluid that is maintained at a stable temperature of approximately 98.6 degrees to a much cooler environment in which they must regulate their own body temperature. Newborns cannot regulate their body temperature in the same ways as adults yet. They produce heat slower due to their small size and lose heat much faster because of a higher ratio of surface area to body volume. They also have limited ability to generate heat by shivering because of their immature musculature. They also cannot quickly constrict their blood vessels in the skin to prevent heat loss due to underdeveloped nervous systems and they have little subcutaneous fat for insulation. Newborns, however, have brown adipose tissue, or brown fat, which can be broken down for thermogenesis. During fetal development, brown fat is accumulated in the back, chest, and shoulders of the fetus in preparation for birth. Brown fat is highly vascularized which allows for faster delivery of oxygen and faster cellular respiration. It also contains a special type of mitochondria that can carry out cellular respiration that produces more heat. The breakdown of brown fat occurs automatically upon exposure to cold, so it is an important heat regulator in newborns.

In adults, the gastrointestinal tract harbors microbiomes — trillions of bacteria that aid in digestion, produce vitamins, and protect from the invasion or replication of pathogens. In stark contrast, the fetal intestine is sterile. The first consumption of breast milk or formula floods the neonatal gastrointestinal tract with beneficial bacteria that begin to establish the bacterial flora.

The fetal kidneys filter blood and produce urine, but the neonatal kidneys are still immature and inefficient at concentrating urine. Therefore, newborns produce very dilute urine, making it particularly important for infants to obtain sufficient fluids from breast milk or formula to prevent dehydration.

28.7 Patterns of Inheritance

Have you ever wondered why you look different from your siblings even though you share the same parents? How are physical characteristics like eye color and hair color determined? The answer to these questions is DNA. The DNA in the sperm and oocyte that combine to form the zygote determines these characteristics.

Introduction

Except for gametes (sperm and oocyte), each human cell has 23 pairs of chromosomes for a total of 46 chromosomes. Each chromosome is composed of a DNA molecule and associated chromosomal proteins. A karyotype represents the complete set of an individual’s chromosomes arranged from largest to smallest [Figure]. In addition, there are 22 pairs of autosomal chromosomes referred to as chromosome 1, chromosome 2, and so on. The 23rd pair is the sex chromosomes that determine the genetic sex of the individual (XX in females and XY in males). Each chromosome carries hundreds or thousands of genes, each of which codes for a specific instruction to assemble a particular protein. All an individual’s genes in their DNA are referred to as the genome. We now have the complete nucleotide sequence of the human genome and know that there are around 20,000 genes.

Figure 28.23: Image of a karyotype of a human male (from Openstax)

The sperm and oocyte each contribute a full complement of 23 chromosomes at fertilization. This is why you inherit one chromosome in each pair from each parent. Homologous chromosomes, such as two chromosomes 1 and two chromosomes 2, contain the same genes in the same locations along their chromosomes. However, these genes are not necessarily identical and may have slightly different sequences of the same gene, which will result in the production of slightly different versions of the protein. These variants of a gene are referred to as alleles. If an individual has two of the same allele of a gene on their homologous chromosomes, they are said to be homozygous. If the alleles are different, they are said to be heterozygous. The activity of an allele can mask the activity of the other allele. The allele with the ability to mask the other allele is called the dominant allele, and the allele that is masked is called the recessive allele. To express a recessive allele there cannot be a dominant allele present. The complete genetic makeup of an individual is referred to as their genotype. The physical characteristics, or traits, which result from the expression of these alleles are called the phenotype. For example, the specific combination of alleles that determines a person’s eye color is their genotype, while the color of their eyes is their phenotype.

When fertilization occurs, each parent contributes one of the two alleles of each gene when producing a zygote. A simple diagram called a Punnett square can be used to illustrate the possible combinations of genes in an offspring if we know the genotype of the parents [Figure below]. For example, let us imagine the case of Rh markers on red blood cells. In the figure below, both parents are heterozygous for the Rh marker gene “D” which encodes the Rh protein in a red blood cell membrane. The dominant allele, represented with a “D,” produces the Rh cell surface marker, and the recessive allele, represented with a “d,” results in the absence of the Rh maker. Both parents have the genotype Dd and, therefore, express the Rh-positive (Rh+) phenotype. Because the parents are heterozygous, they contribute either allele “D” or allele “d” to their gametes with an equal chance. In other words, half of the father’s sperm carries a “D” allele and the other half carries a “d” allele. Same for the mother’s oocytes. The alleles from one parent (Parent 1) are listed on the top of the Punnett square, and the alleles from the other parent (Parent 2) are listed on the slide. The possible genotypes of resulting offspring are in the boxes of the Punnett square. In this case, the possible genotypes and the probabilities of each genotype are the following: DD (1/4 or 25 percent), Dd (1/2 or 50 percent), and dd (1/4 or 25 percent). Because the individuals with DD and Dd genotypes express the Rh marker, the possible phenotypes of the offspring are Rh+ (3/4 or 75 percent) and dd or Rh- (1/4 or 25 percent).

Figure 28.24: Punnett square showing Rh inheritance (Wiki)

Modes of Inheritance

Autosomal Dominant

The Rh marker described in the previous section is an example of autosomal dominant inheritance because the gene is located on one of the autosomal chromosomes, and the Rh+ is a dominant phenotype. Similarly, an autosomal dominant allele of some genes may be responsible for producing a genetic disorder. For example, neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that affects how nerve cells form. An individual with a dominant allele of the NF1 gene may develop multiple light brown spots on the skin, non-malignant tumors on the skin and the eye, bone deformities, and other medical problems that involve the nervous system and other organ systems. Other autosomal dominant disorders include achondroplastic dwarfism, Marfan syndrome, and Huntington’s disease.

Autosomal Recessive

Another mode of inheritance is called autosomal recessive. An autosomal recessive trait will only be expressed if two recessive alleles are inherited. An example of autosomal recessive disorder is cystic fibrosis (CF). Heterozygous individuals are referred to as carriers and will not display symptoms of CF, because the normal allele of the CF gene will compensate. CF affects about 35,000 people in the United States and is characterized by the chronic accumulation of thick and sticky mucus in the lungs, digestive and reproductive tracts that blocks the airways, parts of the digestive tract and the reproductive tract resulting in infertility for males. A child born to two CF carriers would have a 25 percent (one in four) chance of inheriting two CF alleles from the parents (Figure below). On the other hand, a child born to a CF carrier and a non-carrier who is homozygous for normal alleles) would have a zero percent probability of inheriting the CF disease but would have a 50 percent chance of being a CF carrier. Other examples of autosomal recessive disorders include sickle-cell anemia, Tay-Sachs disease, and phenylketonuria (PKU).

Figure 28.25. Autosomal Recessive Inheritance Pattern of Cystic Fibrosis. (from Openstax)

Sex-linked Inheritance

A sex-linked transmission pattern involves genes on the sex chromosomes; X and Y chromosomes. Recall that a male has one X and one Y chromosome, and a female has two X chromosomes. A mother transmits one of her X chromosomes to a child, but a father will transmit either a Y or X chromosome to his child. When a father transmits a Y chromosome, the child is male, and when a father transmits a X chromosome, the child is female.

The Y chromosome is one-third the size of the X chromosome and contains about 55 genes while the X chromosome has about 900 genes. When an abnormal allele for a gene on the X chromosome is dominant over the normal allele, the pattern is described as X-linked dominant. An example of X-linked dominant disorder is vitamin D-resistant rickets. If the father is affected, meaning that he is carrying a dominant disease allele on his X-chromosome, all his daughters will inherit the disease allele, but his sons will not (Figure below Xa). If the mother is heterozygous, all her children, regardless of their sex, will have a 50 percent chance of inheriting the disorder because she can pass either of her X chromosomes to her children (Figure below 28.26b).

Figure 28.26: X-linked Dominant Inheritance Pattern. (Openstax)

X-linked recessive inheritance is much more common because females can be carriers of the recessive allele but have a normal phenotype. One example of X-linked recessive disorder is color blindness. Males will either have color blindness if the X chromosome has the color-blindness allele, or have a normal vision if the X chromosome has the normal allele. On the other hand, a female can be a homozygous normal, a carrier (heterozygous), or affected with color blindness due to being homozygous recessive. The son will only inherit the color-blindness allele from his mother, in which case he will be color blind since he only has one X chromosome and no chance of a dominant allele to mask the recessive allele. However, the daughter will only be affected by the disease if she inherits the color-blindness allele from both parents since females have two X chromosomes (Figure below). This is why color blindness affects far more males than females. Other examples of X-linked recessive disorders are the blood-clotting disorder, hemophilia, and degenerative muscle disorder, Duchenne muscular dystrophy.

Figure 28.27: X-linked Recessive Inheritance Pattern.

Other Patterns of Disorder

Not all genetic disorders are inherited in a simple dominant-recessive pattern. When a heterozygous phenotype is an intermediate between a homozygous dominant phenotype and a homozygous recessive phenotype, it is called incomplete dominance inheritance. In humans, incomplete dominance occurs with one of the genes for hair texture. When one parent passes a curly hair allele (the incompletely dominant allele) and the other parent passes a straight-hair allele, the effect on the offspring will be intermediate, resulting in hair that is wavy.

Another type of inheritance is codominance inheritance. A classic example of codominance is the ABO blood type (Figure below). People are blood type A if they have an allele (IA) for an enzyme that facilitates the production of surface antigen A on their red blood cells. People are blood type B if they have an allele (IB) that allows the production of surface antigen B. Blood type AB individuals are heterozygous for the IA and IB alleles, and as a result, they produce both surface antigens A and B. Therefore, they are both blood type A and blood type B or AB. This is why we say the IA and IB alleles are codominant. The allele i is a recessive allele because people who are homozygous for i alleles do not produce either A or B surface antigens. These individuals have blood type O.

Figure 28.28: Codominance Inheritance Pattern of the ABO blood type (from Wikimedia)

In reality, most traits are controlled by the combined effects of multiple genes. This is referred to as polygenic inheritance. Frequently, environmental factors, as well as genes, produced the combined effects on individuals’ traits, such as skin color, hair color, eye color, height, metabolic rate, and body build. For example, skin color is a good example of a complex trait. Multiple genes affect human skin pigmentation, but we also know from our own experience that sun exposure significantly affects a person’s skin color. Another good example is height. Many genes affect how tall a person becomes. However, the mother’s nutrition during pregnancy, and the nutrition of the child as they grow, greatly affect their height as an adult.

Chromosomal Disorders

A mutation is a change in the normal DNA sequence. A mutation can occur spontaneously from mistakes during DNA replication, or environmental insults such as radiation, viral infection, or exposure to toxic chemicals. A change in the DNA sequence can change the amino acid sequence of a protein produced by reading that sequence and alter the structure and function of the resulting protein. Mutations occurring during meiosis are thought to account for many miscarriages during pregnancy.

Some genetic disorders are caused by the presence of an incorrect number of chromosomes due to nondisjunction, a failure of the chromosomes to separate during meiosis. An example of this type of disorder is Down syndrome. Down syndrome is known as trisomy 21 because an individual with Down syndrome inherited three copies of chromosome 21, rather than two copies. Another example of trisomy is Klinefelter’s syndrome caused by the inheritance of three sex chromosomes: XXY. An individual with Klinefelter’s syndrome is male but has undeveloped testes and is sterile. Turner’s syndrome is another example of the nondisjunction of sex chromosomes. Turner’s syndrome is also known as monosomy because it is caused by having just one copy of the X chromosome. The affected individual is always female because they lack the Y chromosome, but their sexual organs do not mature and they are sterile.

Chapter Summary

Key Terms

acrosomal reaction

release of digestive enzymes by sperm that enables them to burrow through the corona radiata and penetrate the zona pellucida of an oocyte prior to fertilization

acrosome

cap-like vesicle located at the anterior-most region of a sperm that is rich with lysosomal enzymes capable of digesting the protective layers surrounding the oocyte

afterbirth

third stage of childbirth in which the placenta and associated fetal membranes are expelled

allantois

finger-like outpocketing of yolk sac forms the primitive excretory duct of the embryo; precursor to the urinary bladder

allele

alternative forms of a gene that occupy a specific locus on a specific gene

amniotic cavity

cavity that opens up between the inner cell mass and the trophoblast; develops into amnion

autosomal chromosome

in humans, the 22 pairs of chromosomes that are not the sex chromosomes (XX or XY)

autosomal dominant

pattern of dominant inheritance that corresponds to a gene on one of the 22 autosomal chromosomes

autosomal recessive

pattern of recessive inheritance that corresponds to a gene on one of the 22 autosomal chromosomes

blastocoel

fluid-filled cavity of the blastocyst

blastocyst

term for the conceptus at the developmental stage that consists of about 100 cells shaped into an inner cell mass that is fated to become the embryo and an outer trophoblast that is fated to become the associated fetal membranes and placenta

blastomere

daughter cell of a cleavage

Braxton Hicks contractions

weak and irregular peristaltic contractions that can occur in the second and third trimesters; they do not indicate that childbirth is imminent

brown adipose tissue

highly vascularized fat tissue that is packed with mitochondria; these properties confer the ability to oxidize fatty acids to generate heat

capacitation

process that occurs in the female reproductive tract in which sperm are prepared for fertilization; leads to increased motility and changes in their outer membrane that improve their ability to release enzymes capable of digesting an oocyte’s outer layers

carrier

heterozygous individual who does not display symptoms of a recessive genetic disorder but can transmit the disorder to his or her offspring

chorion

membrane that develops from the syncytiotrophoblast, cytotrophoblast, and mesoderm; surrounds the embryo and forms the fetal portion of the placenta through the chorionic villi

chorionic villi

projections of the chorionic membrane that burrow into the endometrium and develop into the placenta

cleavage

form of mitotic cell division in which the cell divides but the total volume remains unchanged; this process serves to produce smaller and smaller cells

codominance

pattern of inheritance that corresponds to the equal, distinct, and simultaneous expression of two different alleles

colostrum

thick, yellowish substance secreted from a mother’s breasts in the first postpartum days; rich in immunoglobulins

conceptus

pre-implantation stage of a fertilized egg and its associated membranes

corona radiata

in an oocyte, a layer of granulosa cells that surrounds the oocyte and that must be penetrated by sperm before fertilization can occur

cortical reaction

following fertilization, the release of cortical granules from the oocyte’s plasma membrane into the zona pellucida creating a fertilization membrane that prevents any further attachment or penetration of sperm; part of the slow block to polyspermy

dilation

first stage of childbirth, involving an increase in cervical diameter

dominant

describes a trait that is expressed both in homozygous and heterozygous form

ductus arteriosus

shunt in the pulmonary trunk that diverts oxygenated blood back to the aorta

ductus venosus

shunt that causes oxygenated blood to bypass the fetal liver on its way to the inferior vena cava

ectoderm

primary germ layer that develops into the central and peripheral nervous systems, sensory organs, epidermis, hair, and nails

ectopic pregnancy

implantation of an embryo outside of the uterus

embryo

developing human during weeks 3–8

embryonic folding

process by which an embryo develops from a flat disc of cells to a three-dimensional shape resembling a cylinder

endoderm

primary germ layer that goes on to form the gastrointestinal tract, liver, pancreas, and lungs

epiblast

upper layer of cells of the embryonic disc that forms from the inner cell mass; gives rise to all three germ layers

expulsion

second stage of childbirth, during which the mother bears down with contractions; this stage ends in birth

fertilization

unification of genetic material from male and female haploid gametes

fertilization membrane

impenetrable barrier that coats a nascent zygote; part of the slow block to polyspermy

fetus

developing human during the time from the end of the embryonic period (week 9) to birth

foramen ovale

shunt that directly connects the right and left atria and helps divert oxygenated blood from the fetal pulmonary circuit

gastrulation

process of cell migration and differentiation into three primary germ layers following cleavage and implantation

genotype

complete genetic makeup of an individual

gestation

in human development, the period required for embryonic and fetal development in utero; pregnancy

heterozygous

having two different alleles for a given gene

homozygous

having two identical alleles for a given gene

human chorionic gonadotropin (hCG)

hormone that directs the corpus luteum to survive, enlarge, and continue producing progesterone and estrogen to suppress menses and secure an environment suitable for the developing embryo

hypoblast

lower layer of cells of the embryonic disc that extend into the blastocoel to form the yolk sac

implantation

process by which a blastocyst embeds itself in the uterine endometrium

incomplete dominance

pattern of inheritance in which a heterozygous genotype expresses a phenotype intermediate between dominant and recessive phenotypes

inner cell mass

cluster of cells within the blastocyst that is fated to become the embryo

involution

postpartum shrinkage of the uterus back to its pre-pregnancy volume

karyotype

systematic arrangement of images of chromosomes into homologous pairs

lactation

process by which milk is synthesized and secreted from the mammary glands of the postpartum female breast in response to sucking at the nipple

lanugo

silk-like hairs that coat the fetus; shed later in fetal development

let-down reflex

release of milk from the alveoli triggered by infant suckling

lightening

descent of the fetus lower into the pelvis in late pregnancy; also called “dropping”

lochia

postpartum vaginal discharge that begins as blood and ends as a whitish discharge; the end of lochia signals that the site of placental attachment has healed

meconium

fetal wastes consisting of ingested amniotic fluid, cellular debris, mucus, and bile

mesoderm

primary germ layer that becomes the skeleton, muscles, connective tissue, heart, blood vessels, and kidneys

morula

tightly packed sphere of blastomeres that has reached the uterus but has not yet implanted itself

mutation

change in the nucleotide sequence of DNA

neural plate

thickened layer of neuroepithelium that runs longitudinally along the dorsal surface of an embryo and gives rise to nervous system tissue

neural tube

precursor to structures of the central nervous system, formed by the invagination and separation of neuroepithelium

neurulation

embryonic process that establishes the central nervous system

notochord

rod-shaped, mesoderm-derived structure that provides support for growing fetus

organogenesis

development of the rudimentary structures of all of an embryo’s organs from the germ layers

parturition

childbirth

phenotype

physical or biochemical manifestation of the genotype; expression of the alleles

placenta

organ that forms during pregnancy to nourish the developing fetus; also regulates waste and gas exchange between mother and fetus

placenta previa

low placement of fetus within uterus causes placenta to partially or completely cover the opening of the cervix as it grows

polyspermy

penetration of an oocyte by more than one sperm

primitive streak

indentation along the dorsal surface of the epiblast through which cells migrate to form the endoderm and mesoderm during gastrulation

prolactin

pituitary hormone that establishes and maintains the supply of breast milk; also important for the mobilization of maternal micronutrients for breast milk

Punnett square

grid used to display all possible combinations of alleles transmitted by parents to offspring and predict the mathematical probability of offspring inheriting a given genotype

quickening

fetal movements that are strong enough to be felt by the mother

recessive

describes a trait that is only expressed in homozygous form and is masked in heterozygous form

sex chromosomes

pair of chromosomes involved in sex determination; in males, the XY chromosomes; in females, the XX chromosomes

shunt

circulatory shortcut that diverts the flow of blood from one region to another

somite

one of the paired, repeating blocks of tissue located on either side of the notochord in the early embryo

syncytiotrophoblast

superficial cells of the trophoblast that fuse to form a multinucleated body that digests endometrial cells to firmly secure the blastocyst to the uterine wall

trait

variation of an expressed characteristic

trimester

division of the duration of a pregnancy into three 3-month terms

trophoblast

fluid-filled shell of squamous cells destined to become the chorionic villi, placenta, and associated fetal membranes

true labor

regular contractions that immediately precede childbirth; they do not abate with hydration or rest, and they become more frequent and powerful with time

umbilical cord

connection between the developing conceptus and the placenta; carries deoxygenated blood and wastes from the fetus and returns nutrients and oxygen from the mother

vernix caseosa

waxy, cheese-like substance that protects the delicate fetal skin until birth

X-linked

pattern of inheritance in which an allele is carried on the X chromosome of the 23rd pair

X-linked dominant

pattern of dominant inheritance that corresponds to a gene on the X chromosome of the 23rd pair

X-linked recessive

pattern of recessive inheritance that corresponds to a gene on the X chromosome of the 23rd pair

yolk sac

membrane associated with primitive circulation to the developing embryo; source of the first blood cells and germ cells and contributes to the umbilical cord structure

zona pellucida

thick, gel-like glycoprotein membrane that coats the oocyte and must be penetrated by sperm before fertilization can occur

zygote

fertilized egg; a diploid cell resulting from the fertilization of haploid gametes from the male and female lines