Reproductive Physiology, Conception, and Fetal Development PDF

Reproductive Physiology, Conception, and Fetal Development 151 Uterus Fallopian tube Infundibulopelvic ligament...

Reproductive Physiology, Conception, and Fetal Development 151 Uterus Fallopian tube Infundibulopelvic ligament Ovarian ligament (suspensory ligament of the ovary) Ovarian vessels Round ligament Ovary Broad ligament Uterosacral ligament Vagina Cardinal ligament FIGURE 8–7 Uterine ligaments. each breast. Suspending the breasts are fibrous tissues, called Cooper Pectoralis minor muscle ligaments, which extend from the deep fascia in the chest outward to First rib just under the skin covering the breast. The left breast is frequently Skin larger than the right. In different racial groups breasts develop at Pectoralis major muscle slightly different levels in the pectoral region of the chest. Fascia of pectoralis muscles In the center of each mature breast is the nipple, a protrusion about 0.5 to 1.3 cm in diameter. The nipple is composed mainly Intercostal muscle of erectile tissue, which becomes more rigid and prominent Alveoli (glandular tissue) during the menstrual cycle, sexual excitement, pregnancy, and lactation. The nipple is surrounded by the heavily pigmented Ductule ring of skin called the areola, 2.5 to 10 cm in diameter. Both the Connective tissue nipple and areola are roughened by small papillae called tubercles stroma of Montgomery. As a baby suckles, these tubercles secrete a fatty Areola substance that helps lubricate and protect the nipple. The breasts are composed of glandular, fibrous, and adipose Nipple tissue. The glandular tissue consists of acini, or alveoli (Figure 8–8), Opening of which are arranged in a series of 15 to 24 lobes separated from lactiferous sinus each other by adipose and fibrous tissue. Each lobe is made up Nipple pores of several lobules, which are made up of many grapelike clusters Ampulla of alveoli around tiny ducts. The lining of these ducts secretes the various components of milk. The ducts from several lobules share Lactiferous duct common openings, called nipple pores, that open on the surface of Suspensory the nipple. The smooth muscle of the nipple causes erection of the ligaments of nipple on contraction. Cooper The biologic function of the breasts is to Adipose tissue provide nourishment and protective maternal antibodies to Sixth rib newborns and infants through the lactation process, and FIGURE 8–8 Anatomy of the breast. be a source of pleasurable sexual sensation. The ovaries produce mature gametes and secrete hormones. Female Reproductive Cycle Ovarian hormones include the estrogens, progesterone, and tes- tosterone. The ovary is sensitive to follicle-stimulating hormone The female reproductive cycle (FRC) is composed of the ovarian (FSH) and luteinizing hormone (LH). The relative proportions cycle, during which ovulation occurs, and the menstrual cycle, of these hormones control the events of both ovarian and men- during which menstruation occurs. These two cycles take place strual cycles and thus are responsible for the cyclic changes that simultaneously (Figure 8–9). allow pregnancy to occur. Effects of Female Hormones ESTROGENS Menstruation is an orderly process under neurohormonal control. Estrogens are hormones that are associated with those charac- Each month, multiple oocytes mature, with one rupturing from the teristics contributing to “femaleness,” including breast alveolar ovary and entering the fallopian tube. The ovary, vagina, uterus, lobule growth and duct development. They also assist in the and fallopian tubes are major target organs for female hormones. maturation of the ovarian follicles and cause the endometrial 152 Chapter 8 Anterior pituitary FSH LH Primary Secondary Graafian Corpus Degenerating Ovulation Ovarian follicle follicle follicle lueumt corpus luteum cycle Day of cycle 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 1 2 3 4 Ovarian hormones Estrogen Progesterone Glands Arteries Endometrial Veins changes during the menstrual Functional cycle layer Basal layer Men- Uterine Phases Menstrual Proliferative Secretory strual Ovarian Phases Follicular Luteal Days 1 4 6 8 12 14 16 20 24 28 FIGURE 8–9 Female reproductive cycle: Interrelationships of hormones with the three phases of the uterine cycle and the two phases of the ovarian cycle in an ideal 28-day cycle. mucosa to proliferate following menstruation. The amount The ovaries secrete the largest amounts of estrogens; how- of estrogens is greatest during the proliferative (follicular or ever, the adrenal cortex (extraglandular sites) produces minute estrogenic) phase of the menstrual cycle. Estrogens cause the amounts of estrogens in nonpregnant women and the fat cells uterus to increase in size and weight because of increased gly- produce a secondary estrogen. cogen, amino acids, electrolytes, and water. Blood supply is Estrogens have effects on many hormones and other car- expanded as well. Under the influence of estrogens, myome- rier proteins, such as contributing to the increased amount of trial contractility increases in both the uterus and the fallopian protein-bound iodine in pregnant women and women who use tubes, and uterine sensitivity to oxytocin increases. Estrogens oral contraceptives containing estrogen. inhibit FSH production and stimulate LH production. The major estrogenic effects are due primarily to three estrogens: PROGESTERONE Estrone, β-estradiol, and estriol, with β-estradiol being the Progesterone is secreted by the corpus luteum and is found in major estrogen. greatest amounts during the secretory (luteal or progestational)  Reproductive Physiology, Conception, and Fetal Development 153 phase of the menstrual cycle. Progesterone is often called the the corpus luteum. The lutein cells secrete large amounts of hormone of pregnancy because its effects on the uterus allow preg- progesterone with smaller amounts of estrogen. (Concurrently, nancy to be maintained. Under the influence of progesterone the the excessive amounts of progesterone are responsible for the following occur: secretory phase of the uterine cycle.) On day 7 or 8 follow- ing ovulation, the corpus luteum begins to involute, losing its Vaginal epithelium proliferates. secretory function. The production of both progesterone and Cervix secretes thick, viscous mucus. estrogen is severely diminished. The anterior pituitary responds Breast glandular tissue increases in size and complexity. with increasingly large amounts of FSH; a few days later, LH Breasts prepare for lactation. production begins. New follicles become responsive to another ovarian cycle and begin maturing. Temperature rises about 0.3°C to 0.6°C (0.5°F to 1.0°F), which accompanies ovulation and persists throughout the secre- OVARIAN CYCLE tory phase of the menstrual cycle. The ovarian cycle has two phases: The follicular phase (days 1 to 14) PROSTAGLANDINS and the luteal phase (days 15 to 28 in a 28-day cycle). Figure 8–10 depicts the changes that the follicle undergoes during the ovarian Prostaglandins (PGs) are hormones produced by the cells of cycle. In women whose menstrual cycles vary, usually it is only the endometrium. The two primary types of prostaglandins the length of the follicular phase that varies because the luteal are groups E and F. Generally, PGE relaxes smooth muscles phase is of fixed length (Blackburn, 2018; Cunningham et al., and is a potent vasodilator; PGF is a potent vasoconstrictor and 2022). During the follicular phase, the immature follicle matures increases the contractility of muscles and arteries. Although as a result of FSH. Within the follicle, the oocyte grows. their primary actions seem antagonistic, their basic regulatory A mature graafian follicle appears about the 14th day under functions in cells are achieved through an intricate pattern of dual control of FSH and LH. It is a large structure, measuring reciprocal events. about 5 to 10 mm, and produces increasing amounts of estrogen. Prostaglandin production increases during follicular matu- In the mature graafian follicle, the cells surrounding the fluid- ration, is dependent on gonadotropins, and seems to be critical filled antral cavity are called granulosa cells. The mass of granu- to follicular rupture. Extrusion of the ovum, resulting from fol- losa cells surrounding the oocyte and follicular fluid is called the licular swelling and increased contractility of the smooth muscle cumulus oophorus. In the fully mature graafian follicle, the zona in the theca layer of the mature follicle, is thought to be caused pellucida, a thick elastic capsule, develops around the oocyte. by PGF2α. Significant amounts of PGs are found in and around Just before ovulation, the mature oocyte completes its first the follicle at the time of ovulation. meiotic division (see a description of meiosis later in the chapter). As a result of this division, two cells are formed: A small cell Neurohormonal Basis of the Female called a polar body and a larger cell called the secondary oocyte. The Reproductive Cycle secondary oocyte matures into the ovum. As the graafian follicle matures and enlarges, its walls thin The female reproductive cycle is controlled by complex inter- and it travels outward to the surface of the ovary. This surface actions between the nervous and endocrine systems and their has a blister-like protrusion 10 to 15 mm in diameter, where the target tissues. These interactions involve the hypothalamus, ante- secondary oocyte, polar body, and follicular fluid are pushed out. rior pituitary, and ovaries. The ovum is discharged near the fimbria of the fallopian tube The hypothalamus secretes gonadotropin-releasing and is pulled into the tube to begin its journey toward the uterus hormone (GnRH) to the pituitary gland in response to signals (see Figure 8–6). received from the central nervous system. This releasing hormone is often called follicle stimulating hormone–releasing hormone (FSHRH) or luteinizing hormone–releasing hormone (LHRH) Germinal (Blackburn, 2018). In response to GnRH, the anterior pituitary epithelium Zona secretes the gonadotropic hormones FSH and LH. pellucida Artery FSH is primarily responsible for the maturation of the ovarian Primary Developing follicle. As the follicle matures, it secretes increasing amounts Vein follicle follicles Antrum of estrogen, which enhance the development of the follicle. containing (This estrogen is also responsible for the rebuilding/proliferation follicular fluid phase of the endometrium after it is shed during menstruation.) Final maturation of the follicle will not come about with- Mature out the action of LH. The anterior pituitary’s production of graafian LH increases 6-fold to 10-fold as the follicle matures. The Corpus follicle peak production of LH can precede ovulation by as much as albicans 10 to 12 hours (Blackburn, 2018). LH is also responsible for “luteinizing” the increase in production of progesterone by the Stroma granulosa cells of the follicle. As a result, estrogen production Tunica declines and progesterone secretion continues. Thus, estrogen albuginea levels fall a day before ovulation; tiny amounts of the hormones Mature inhibin and progesterone are in evidence (Blackburn, 2018). corpus Blood Lutein Ovulation takes place following the very rapid growth of the luteum clot Discharged cells Ruptured follicle—as the sustained high level of estrogen diminishes and ovum Fibrin follicle progesterone secretion begins. The ruptured follicle undergoes rapid change, complete FIGURE 8–10 Various stages of development of the ovarian luteinization is accomplished, and the mass of cells becomes follicles. 154 Chapter 8 In some women, ovulation is accompanied by midcycle when they become pregnant. Emotional and physical factors such pain, known as mittelschmerz. This pain may be caused by a thick as illness, excessive fatigue, stress or anxiety, and rigorous exercise tunica albuginea or by a local peritoneal reaction to the expelling programs can alter the cycle interval. Certain environmental factors of the follicular contents. Vaginal discharge may increase during such as temperature and altitude may also affect the cycle. The ovulation, and a small amount of blood (midcycle spotting) may duration of menses is from 2 to 8 days, with the blood loss averag- be discharged as well. ing 25 to 60 mL and the loss of iron averaging 0.5 to 1 mg daily. The body temperature increases about 0.3°C to 0.6°C (0.5°F to A review of the endometrium and its arterial blood supply 1°F) 24 to 48 hours after the time of ovulation. It remains elevated will provide further understanding of the menstrual process until the day before menstruation begins. There may be an accom- (Figure 8–11). Blood flow from the spiral arterioles in the panying sharp basal body temperature drop just before the increase. superficial endometrium is reduced, leading to a lack of blood These temperature changes are useful clinically to determine the and oxygen, which in turn produces tissue death (necrosis) and approximate time ovulation occurs (Blackburn, 2018). discharge of the superficial endometrium (menses). At the same Generally, the ovum takes several minutes to travel through time, the straight arterioles provide the basal endometrium with the ruptured follicle to the fallopian tube opening. The contrac- sufficient blood flow to maintain this layer of the endometrium tions of the tube’s smooth muscle and its ciliary action propel and the endometrial glands (or seeds) that are responsible for the the ovum through the tube. The ovum remains in the ampulla, generation of the endometrium in the next female reproductive where, if it is fertilized, cleavage can begin. The ovum is thought or menstrual cycle (see Figure 8–9). Bleeding is controlled by to be fertile for only 6 to 24 hours. It reaches the uterus 72 to vasospasm of the straight basal arterioles, resulting in coagulative 96 hours after its release from the ovary. necrosis at the vessel tips (Cunningham et al., 2022). The luteal phase begins when the ovum leaves its follicle. The uterine (menstrual) cycle has three phases: The menstrual Under the influence of LH, the corpus luteum develops from phase, proliferative phase, and secretory phase. Menstruation the ruptured follicle. Within 2 or 3 days, the corpus luteum occurs during the menstrual phase. Some endometrial areas are becomes yellowish and spherical and increases in vascularity. shed, whereas others remain. Some of the remaining tips of the If the ovum is fertilized and implants in the endometrium, the endometrial glands begin to regenerate. The endometrium is in fertilized egg begins to secrete human chorionic gonadotropin a resting state following menstruation. Estrogen levels are low, (hCG), which is needed to maintain the corpus luteum. If fertil- and the endometrium is 1 to 2 mm thick. During this part of the ization does not occur, within about a week after ovulation, the cycle the cervical mucus is scanty, viscous, and opaque. corpus luteum begins to degenerate, eventually becoming a con- The proliferative phase begins when the endometrial glands nective tissue scar called the corpus albicans. With degeneration enlarge, becoming twisted and longer, in response to increasing comes a decrease in estrogen and progesterone. This allows for amounts of estrogen. The blood vessels become prominent and an increase in LH and FSH, which triggers the hypothalamus. dilated, and the endometrium increases in thickness 6-fold to 8-fold. This gradual process reaches its peak just before ovula- UTERINE (MENSTRUAL) CYCLE tion. The cervical mucus becomes thin, clear, watery, and more Menstruation is cyclic uterine bleeding in response to cyclic alkaline, making the mucus more favorable to spermatozoa. As hormonal changes. Menstruation occurs when the ovum is ovulation nears, the cervical mucus shows increased elasticity not fertilized and begins about 14 days after ovulation (in an and its pH increases from below 7 to 7.5 at the time of ovulation. ideal 28-day cycle) in the absence of pregnancy. The menstrual The secretory phase follows ovulation. The endometrium, discharge, also referred to as the menses or menstrual flow, is under estrogenic influence, undergoes slight cellular growth. composed of blood mixed with cervical and vaginal secretions, Progesterone, however, causes such marked swelling and bacteria, mucus, leukocytes, and other cellular debris. The growth that the epithelium is warped into folds (Figure 8–12). menstrual discharge is dark red and has a distinctive odor. The amount of tissue glycogen increases. The glandular epithelial Menstrual parameters vary greatly among individuals. cells begin to fill with cellular debris, become twisted, and dilate. Generally, menstruation occurs every 29 days but varies from 21 The glands secrete small quantities of endometrial fluid in prepa- to 35 days. Some women normally have longer cycles, which can ration for a fertilized ovum. The vascularity of the entire uterus skew standard calculations of the estimated date of birth (EDB) increases greatly, providing a nourishing bed for implantation. Endometrial gland (“seed”) Radial artery Spiral (coiled) arteriole Straight arteriole Uterine artery Arcuate artery Radial artery Myometrium Endometrium FIGURE 8–11 Blood supply to the endometrium (cross-sectional view of the uterus).  Reproductive Physiology, Conception, and Fetal Development 155 A B FIGURE 8–12 Scanning electron micrographs of the uterine lining during the secretory phase of the uterine cycle and at the time of blastocyst implantation. A. A blastocyst begins implanting in the wall of the uterus. B. Light micrograph (LM) of an 11-day-old implantation site in the human endometrium (uterine lining) showing bilaminar embryo, amnion, and surrounding placental trophoblasts. Magnification unknown. SOURCE: A. Stocktrek Images, Inc./Alamy; B. David Mack/Science Source. If implantation occurs, the endometrium, under the influence of progesterone, continues to develop and become even thicker Male Reproductive System (implantation is discussed later in the chapter). The primary reproductive functions of the male genitals are to If fertilization does not occur, the menstrual phase (days 27–28) produce and transport the male sex cells (sperm) through and begins. The corpus luteum begins to degenerate and, as a result, eventually out of the genital tract into the female genital tract. both estrogen and progesterone levels fall. Extensive vascular The male reproductive system consists of the external and inter- changes also occur. Small blood vessels rupture, and the spiral nal genitals (Figure 8–13). arteries constrict and retract, causing a deficiency of blood in the endometrium, which becomes pale. Then there is escape of blood External Genitals into the stromal cells of the uterus. The menstrual flow (days 1–6) The two external reproductive organs are the penis and the scrotum. begins, thus beginning the menstrual cycle again. After menstru- ation, the basal layer remains, so that the tips of the glands can PENIS regenerate the new functional endometrial layer. See Key Facts to The penis is an elongated, cylindrical structure consisting of a Remember: Summary of the Female Reproductive Cycle. body, termed the shaft, and a cone-shaped end called the glans. KEY FACTS TO REMEMBER Summary of the Female Reproductive Cycle Ovarian Cycle Cervical mucus at ovulation is clear, thin, watery, and alkaline; it is more favorable to sperm and has increased elasticity on microscopic exam. Follicular phase (days 1–14): Primordial follicle matures under influence of FSH and LH up to the time of ovulation. Just before ovulation, body temperature may drop slightly, then at ovulation basal body temperature increases 0.3° to 0.6°C (0.5° to 1.0°F). Luteal phase (days 15–28): Ovum leaves follicle; corpus luteum develops under LH influence and produces high levels of progesterone and low Mittelschmerz and/or midcycle spotting may occur. levels of estrogen. Secretory phase (days 15–26): Estrogen drops sharply, and progesterone dominates. Menstrual Cycle Vascularity of entire uterus increases. Menstrual phase (days 1–6): Estrogen levels are low. Tissue glycogen increases, and the uterus is made ready for implantation. Cervical mucus is scant, viscous, and opaque. Menstrual phase begins (days 27–28): Both estrogen and progesterone Endometrium is shed. levels drop. Proliferative phase (days 7–14): Endometrium and myometrium Spiral arteries undergo vasoconstriction. thickness increases. Endometrium becomes pale; blood vessels rupture. Estrogen peaks just before ovulation. Blood escapes into uterine stromal cells, gets ready to be shed.