I. Reproductive Anatomy (p. 1047; fig. 28.1; TR 916, 917)

A. Sex Differentiation (p. 1047)

1. The female reproductive tract develops not because of hormone action but because of the absence of testosterone and mullerian-inhibiting factor.

2. In the absence of these influences, the mesonephric duct degenerates, while the phallus becomes a clitoris, the urogenital folds develop into labia minora, and the labioscrotal folds develop into labia majora. The paramesonephric duct becomes the uterus, uterine tubes, and vagina.

B. The Ovary (p. 1047; fig. 28.2; TR 918, 919 )

1. The female gonads are the ovaries, which produce egg cells (ova) and sex hormones.

2. The interior of the ovary is distinctly divided into an outer cortex, where the germ cells develop, and a central medulla occupied by the major arteries and veins.

3. Each egg cell develops in its own fluid-filled follicle and is released by ovulation.

4. The ovary is held in place by the ovarian, suspensory, and broad ligaments as well as a peritoneal fold called the mesovarium. (fig. 28.3; TR 920, 921)

5. The ovary is supplied with an ovarian artery, ovarian veins, and ovarian nerves, which travel through the suspensory ligament.

C. Secondary Sex Organs (Genitalia) (p. 1047)

1. The internal genitalia are the uterine tubes, uterus, and vagina, which constitute a duct system from the vicinity of the ovary to the outside of the body.

2. The external genitalia include principally the clitoris, labia minora, and labia majora.

3. The uterine tube (oviduct or fallopian tube) is a canal 10 cm long leading from the ovary to the uterus. It has a trumpet-shaped infundibulum with projections called fimbriae.

a. The wall of the uterine tube is well endowed with smooth muscle, and its extremely folded mucosa has ciliated cells. (fig. 28.4)

b. The cilia beat toward the uterus and, with the help of muscular contractions of the tube, convey the egg in that direction.

4. The uterus is a thick, muscular chamber that harbors the embryo, provides a source of nutrition, and expels the fetus at the end of its development. The uterus is somewhat pear-shaped, and its cylindrical inferior end is called the cervix.

a. The uterine wall consists of three layers: the perimetrium myometrium, and endometrium.

i. The perimetrium on the outside is the serosa.

ii. The middle myometrium is a layer of smooth muscle constituting most of the wall. The myometrium has bundles of smooth muscle running in all directions, but it is less muscular and more fibrous near the cervix. The cervix itself is almost entirely collagenous.

iii. The endometrium is the mucosa. The superficial half to two-thirds of it, called the stratum functionalis, is shed during each menstrual period. The deeper layer, called the stratum basalis, stays behind and regenerates a new functionalis in the next cycle. (fig. 28.6)

b. A uterine artery arises from each internal iliac artery and gives off several branches that penetrate into the myometrium and lead to arcuate arteries. These give rise to smaller arteries than enter the endometrium and produce spiral arteries. Spiral arteries rhythmically constrict and dilate, making the mucosa alternately blanch and flush with blood. (fig. 28.7; TR 922)

5. The vagina (birth canal) is a tube 8–10 cm long that allows for the discharge of menstrual fluid, receipt of the penis and semen, and birth of a baby. The vaginal wall is thin but very distensible.

a. The vagina tilts posteriorly between the urethra and rectum; the urethra is embedded in its anterior wall.

b. The vaginal epithelium is simple cuboidal in childhood, but the estrogens of puberty stimulate it to transform into a stratified squamous epithelium. The epithelial cells are rich in glycogen. Bacteria ferment this to lactic acid, resulting in a low vaginal pH.

6. The vulva (pudendum) includes the mons pubis, labia majora and minora, and clitoris.

a. Pubic hair grows on the mons pubis and lateral surfaces of the labia majora at puberty. (fig. 28.8; TR 923)

b. The clitoris is structured like a miniature penis except that it is almost entirely internal, has no corpus spongiosum, and does not enclose the urethra.

7. On each side of the vagina is a pea-sized greater vestibular (Bartholin) gland with a short duct opening into the vestibule or lower vagina. These glands are homologous to the bulbourethral glands of the male. They keep the vagina moist and provide most of the lubrication for intercourse.

D. Secondary Sex Characteristics (p. 1053)

1. The Breasts (figs. 28.9, 28.10; TR 924, 925)

a. The breast is a mound of tissue overlying the pectoralis major. It has two principal regions: the conical to pendulous body, with the nipple at its apex, and an extension toward the armpit called the axillary tail. Lymphatics of the axillary tail are especially important as a route of breast cancer metastasis.

b. The nipple is surrounded by a circular colored zone, the areola. It has sparse hairs and areolar glands, visible as small bumps on the surface. These are intermediate between sweat glands and mammary glands in development. When a woman is nursing, their secretion minimizes chapping and cracking of the areola.

c. Internally, the nonlactating breast consists mostly of adipose and collagenous tissue and contains very little mammary gland. It does have a system of ducts through its connective tissue stroma converging on the nipple.

d. When the mammary gland develops during pregnancy, it exhibits 15–20 lobes arranged radially around the nipple, each drained by a lactiferous duct. These dilate to form a lactiferous sinus opening into the nipple.

e. Breast cancer occurs in one out of every eight or nine American women and is one of the leading causes of female mortality.

i. Symptoms of breast cancer include a palpable lump, puckering of the skin, changes in skin texture, and drainage from the nipple.

ii. Some breast cancer tumors are stimulated by estrogen. Other risk factors include aging, exposure to ionizing radiation and carcinogenic chemicals, excessive alcohol and fat intake, and smoking. Two breast cancer genes have been discovered, but most breast cancer is not hereditary.

iii. The majority of tumors are discovered by breast self-examination (BSE), which should be done routinely every month. Mammograms, however, can detect tumors too small to be noticed by BSE. (fig. 28.11)

iv. Treatment of breast cancer is usually by lumpectomy or simple mastectomy. Surgery is generally followed by radiation or chemotherapy, and estrogen-sensitive tumors may be treated with an estrogen blocker such as tamoxifen.

II. Puberty and Menopause (p. 1056)

A. Puberty (p. 1056)

1. Puberty begins at ages 9 to 10 for most girls in the United States and Europe but significantly later in other countries. Rising levels of GnRH stimulate the anterior pituitary to produce FSH and LH, the same as in the male. FSH stimulates the development of the ovarian follicles, which in turn secrete estrogens, progesterone, inhibin, and a small amount of androgen.

a. These hormone levels rise gradually from ages 8 to 12 and then more sharply in the early teens. The estrogens are feminizing hormones with widespread effects on the body. They include estradiol (the most abundant), estriol, and estrone.

b. The earliest notable change is thelarche, the development of the breasts. Soon after this comes pubarche, development of the pubic and axillary hair, sebaceous glands, and apocrine glands. Next comes menarche, the first menstrual period. Menarche does not occur until a girl has reached 17% body fat, so it can be delayed in girls who are very athletic. Adult menstruation generally ceases if a woman drops below 22% body fat. Most girls begin ovulating about a year after they begin menstruating.

2. Estradiol stimulates growth of the ovaries and secondary sex organs. It stimulates osteoblasts, causing a growth spurt and widening of the pelvis. Estradiol is largely responsible for the feminine physique.

3. Progesterone acts primarily on the uterus, preparing it for possible pregnancy. Estrogens and progesterone also suppress FSH and LH through negative feedback. Inhibin selectively suppresses FSH secretion.

B. Climacteric and Menopause (p. 1057)

1. Women, like men, go through a midlife change in hormone secretion called the climacteric.

2. With age, the ovaries have fewer remaining follicles, and those that do remain are less responsive to gonadotropins. Consequently, they secrete less estrogen and progesterone. Without these steroids, the uterus, vagina, and breasts atrophy.

3. Menopause is the cessation of menstrual cycles, usually occurring between the ages of 45 and 55. The average age has increased steadily in the last century and is now about 52.

III. Oogenesis and the Sexual Cycle (p. 1058)

A. Oogenesis (p. 1058; fig. 28.12; TR 926)

1. Egg production, called oogenesis, is a distinctly cyclic event.

2. The female germ cells arise from the yolk sac of the embryo. They colonize the gonadal ridges and then differentiate into oogonia. Oogonia multiply until the fifth month of fetal development, reach 6–7 million in number, and then go into a state of arrested development until shortly before birth. At that time, some of them transform into primary oocytes and go as far as meiosis I.

3. Most primary oocytes undergo a process of degeneration called atresia. Only 2 million remain at the time of birth, and by puberty, only 400,000 remain.

4. Beginning in adolescence, FSH stimulates the primary oocytes to complete meiosis I, which yields two haploid daughter cells of unequal size. One becomes the egg, with a large amount of cytoplasm. The other, a polar body, serves only as a dumping ground for the extra set of chromosomes.

5. The secondary oocyte proceeds as far as metaphase II and then arrests until ovulation. If it is fertilized, it completes meiosis II and produces a second polar body. The large remaining egg unites its chromosomes with those of the sperm and produces a zygote.

B. The Sexual Cycle (p. 1058; fig. 28.13; TR 927; table 28.1)

1. The female sexual cycle is a monthly sequence of changes caused by shifting patterns of hormone secretion. The discussion here is based on a 28-day cycle.

2. The average cycle begins with a 2-week follicular phase, which is divided into a menstrual phase and a preovulatory phase.

a. During the menstrual phase (days 1–5), primordial follicles develop into primary and then secondary follicles. (fig. 28.14)

b. The preovulatory phase (days 6–13) is characterized by rapid growth of one follicle and atresia of the lagging follicles.

c. As the graafian follicle matures, the primary oocyte completes meiosis I and becomes a secondary oocyte. This cell begins meiosis II but stops at metaphase II. It is now ready for ovulation.

3. Ovulation, the release of the oocyte, typically occurs on day 14 and is triggered by shifting patterns of hormone secretion.

a. Ovulation is triggered by shifting patterns of hormone secretion. Estrogen stimulates LH secretion, and LH triggers ovulation. (fig. 28.15; TR 928)

b. The oocyte and its attendant cells are normally swept up by the ciliary current and taken into uterine tube, although many fall into the pelvic cavity and die. (fig. 28.16)

c. An oocyte has only 24 hours to be fertilized. The chance of fertilization is enhanced because the cervical mucus changes at the time of ovulation, becoming thinner and more stringy.

4. The postovulatory phase spans days 15 to 28. The first 12 days are the luteal (secretory) phase, and the last 2 are the premenstrual (ischemic) phase.

a. During the luteal phase, the ovulated follicle becomes a structure called the corpus luteum. If pregnancy occurs, the corpus luteum remains active for about 3 months. In the absence of pregnancy, it begins to degenerate in about 10 days because rising progesterone output inhibits further release of FSH and LH. Without LH, the corpus luteum atrophies (involution).

b. During the premenstrual phase, necrotic tissue falls away from the uterine wall, mixes with blood in the lumen, and forms the menstrual fluid.

5. The first day of vaginal discharge is considered day 1 of the new cycle.

a. Menstrual fluid contains fibrolysin; therefore, it normally does not clot.

b. Involution of the corpus luteum ends the negative feedback effect of progesterone on the hypothalamus. Thus, GnRH secretion rises, followed by FSH and a new crop of ovarian follicles.

IV. Female Sexual Response (p. 1065; fig. 28.17; TR 929, 930)

A. The four stages of female response suggested by Masters and Johnson are: excitement, plateau, orgasm, and resolution.

B. Excitement and Plateau (p. 1065)

1. Female excitement is marked by myotonia, vasocongestion, and increases in heart rate, blood pressure, and respiratory rate. The labia minora become quite congested, and the labia majora become reddened and enlarged.

2. The vaginal wall becomes purple due to hyperemia, and serous fluid called vaginal transudate seeps through the wall into the canal.

3. The uterus, which normally tilts forward over the urinary bladder, stands more erect during excitement, and the cervix withdraws from the vagina.

4. In plateau, the uterus is nearly vertical and extends into the false pelvis. This is called the tenting effect.

C. Orgasm (p. 1065)

1. Late in plateau, many women experience involuntary pelvic thrusting.

2. The orgasmic platform gives three to five strong contractions about 0.8 seconds apart.

D. Resolution (p. 1067)

1. During resolution, the uterus drops forward to its resting position and the cervix protrudes into the vagina. The orgasmic platform quickly relaxes.

2. Unlike men, women do not have a refractory period and may quickly experience additional orgasms.

V. Pregnancy and Childbirth (p. 1067)

A. Prenatal Development (p. 1067)

1. Fertilization must occur in the distal half of the uterine tube if it is to occur at all, since an unfertilized egg does not live long enough to reach the uterus alive.

2. Soon after it reaches the uterus, the conceptus becomes a blastocyst, which consists of an inner cell mass destined to develop into the embryo and an outer trophoblast that plays various supporting roles. The trophoblast is responsible for implantation in the uterine lining and later gives rise to the placenta.

B. Hormones of Pregnancy (p. 1067; fig. 28.18; TR 931; table 28.2)

1. Human chorionic gonadotropin (HCG) is secreted by the trophoblast cells. Its presence is the basis of pregnancy tests. HCG secretion peaks around 10–12 weeks and then falls. It stimulates growth of the corpus luteum, which doubles in size and secretes increasing amounts of progesterone and estrogen.

2. Estrogen secretion increases to about 30 times the normal amount by the end of gestation. Estrogens stimulate tissue growth in the fetus and mother. They cause the mother's uterus and external genitalia to enlarge, the mammary ducts to grow, and the breasts to increase to nearly twice their normal size. They make the pubic symphysis more elastic and the sacroiliac joints more limber.

3. The placenta secretes a great deal of progesterone. This, coupled with estrogen secretion, suppresses the secretion of FSH and LH, preventing follicles from developing during pregnancy. Progesterone also suppresses uterine contractions and prevents menstruation.

4. The amount of human chorionic somatomammotropin (HCS) secreted in pregnancy is several times that of all other hormones combined. The placenta begins secreting HCS around the fifth week, and HCS output increases steadily from then until term. It promotes the release of free fatty acids from the mother's adipose tissue among other unknown functions.

5. Pregnancy affects many other aspects of endocrine function. A woman's pituitary gland grows by 50% during pregnancy and produces markedly elevated levels of thyrotropin, prolactin, and ACTH. The thyroid also becomes larger.

C. Adjustments to Pregnancy (p. 1069)

1. Many women experience morning sickness and nausea during the early stages of pregnancy, and constipation and heartburn later in the pregnancy. The basal metabolic rate increases by 15% during the second half of gestation. During the last trimester, the fetus needs more nutrients than the mother's digestive tract can absorb. In preparation for this, the placenta stores nutrients early in gestation and releases them in the final trimester. The demand is especially high for protein, iron, calcium, and phosphates.

2. The mother's blood volume rises about 30% during pregnancy due to fluid retention and hemopoiesis; she eventually has 1 to 2 L of extra blood.

3. Oxygen demands are about 20% higher by late pregnancy in order to supply the fetus; consequently, the respiratory rate increases to compensate.

4. Aldosterone and the other steroids of pregnancy promote water and salt retention by the kidneys. Nevertheless, urine output increases slightly because the glomerular filtration rate increases by 50%. The mother must dispose of both her own and the fetus's wastes.

5. The skin must grow to accommodate expansion of the abdomen and breasts, and is often marked by stretch marks from stretching of the dermis.

6. The uterus weighs about 50 g when a woman is not pregnant and 1,100 g by the end of pregnancy. (table 28.3)

D. Childbirth (p. 1070; fig. 28.19; TR 932)

1. The process of giving birth is called parturition.

2. Uterine Contractility

a. Over the course of gestation, the uterus exhibits relatively weak Braxton Hicks contractions.

b. During the first 6–7 months, progesterone inhibits uterine contractions, but by the seventh month, progesterone secretion levels off or declines slightly. The secretion of estrogen, which stimulates uterine contractions, continues to rise.

c. As the pregnancy reaches full term, the posterior pituitary releases more oxytocin and promotes labor by stimulating the muscle of the myometrium and by stimulating fetal tissue to secrete prostaglandins, which are synergists of oxytocin.

d. Uterine stretching is also thought to play a role in initiating labor.

3. Labor Contractions

a. Labor contractions begin about 30 minutes apart. As labor progresses, they become more intense and eventually occur every 1 to 3 minutes. Each contraction sharply reduces maternal blood flow to the placenta, so the uterus must periodically relax to restore blood flow and oxygen delivery to the fetus.

b. According to the positive feedback theory of labor, true labor contractions are induced by stretching of the cervix, which in turn causes the uterus to stretch and contract. There is a self-amplifying cycle of stretch and contraction.

c. As labor progresses, a woman feels a growing urge to "bear down." Contraction of uterine and skeletal muscles of the abdomen aid in expelling the fetus.

d. The pain of labor is mainly due at first to ischemia of the myometrium. The pain of human childbirth, as compared to the relative ease with which other animals give birth, is an evolutionary product of the narrowing of the pelvic outlet as hominids adopted bipedal locomotion.

4. Labor occurs in three stages. (fig. 28.20; TR 933)

a. The first stage of labor, dilation, is the longest, and involves effacement and dilation of the cervix to 10 cm.

b. The second stage of labor is the expulsion of the fetus and may last from 1 minute to 30 minutes in first-time mothers. Delivery of the head is the most difficult part, with the rest of the body following much more easily. (fig. 28.21)

c. During the placental stage, the uterus continues to contract after expulsion of the baby. About 350 mL of blood is typically lost at this stage, but contractions of the myometrium compress the blood vessels and prevent more extensive bleeding.

E. Puerperium (p. 1073)

1. The first six weeks postpartum are called the puerperium, a period in which the mother's anatomy and physiology stabilize and the reproductive organs shrink to their condition prior to pregnancy.

2. Shrinking of the uterus, called involution, is achieved through autolysis of uterine cells by their own lysosomal enzymes.

VI. Lactation (p. 1074)

A. Development of the Mammary Glands in Pregnancy (p. 1074)

1. Lactation, the synthesis and ejection of milk from the mammary glands, can continue indefinitely as long as the breast is stimulated by a nursing infant or breast pump.

2. The high estrogen level in pregnancy causes the ducts of the mammary gland to grow and branch extensively. Once the ducts are complete, progesterone stimulates the budding and development of acini at the ends of the ducts.

B. Colostrum and Milk Synthesis (p. 1074)

1. In late pregnancy, the mammary acini and ducts become distended with a secretion called colostrum. This is similar to breast milk in protein and lactose content but contains about one-third less fat. It is the infant's only natural source of nutrition for the first 2 to 3 days postpartum. Colostrum has a thin, watery consistency and a cloudy, yellowish color.

2. A major benefit of colostrum is that it contains immunoglobulins, especially IgA, which may protect the infant against gastroenteritis.

3. Milk synthesis is promoted by prolactin, a hormone of the anterior pituitary gland. (fig. 28.22; TR 934)

C. Milk Ejection (p. 1075)

1. Milk ejection is mediated by a neuroendocrine reflex. The infant's suckling stimulates nerve endings of the nipple and areola, which in turn signal the hypothalamus and posterior pituitary to release oxytocin. Oxytocin stimulates myoepithelial cells, which form a basketlike mesh around each gland acinus. (fig. 28.23)

2. The infant does not get any milk for the first 30 to 60 seconds of suckling, but milk soon fills the ducts and lactiferous sinuses and is then easily sucked out.

D. Breast Milk (p. 1075)

1. Colostrum and milk have a laxative effect that helps clear the neonate intestine of meconium, a sticky, greenish-black fecal matter composed of bile, epithelial cells, and other wastes. By clearing bile and bilirubin from the system, breast-feeding also reduces the incidence and degree of jaundice in neonates.

2. A woman is at greater risk of bone loss when breast-feeding than when she is pregnant.

3. Cow’s milk is not a good substitute for human milk. It contains one-third less lactose, but three to five times as much protein and minerals. (table 28.4; TR 935)

VII. Disorders of Pregnancy (p. 1076; table 28.5)