Female Reproductive Physiology Part 3 PDF

FEMALE REPRODUCTIVE PHYSIOLOGY part 3 sergeenko FEMALE REPRODUCTIVE PHYSIOLOGY The female gonads are the ovaries, which, together with the uterus and the fallopian tubes, constitute the female reproductive tract. Ovaries functions: oogenesis and secretion of the female sex s...

FEMALE REPRODUCTIVE PHYSIOLOGY part 3 sergeenko FEMALE REPRODUCTIVE PHYSIOLOGY The female gonads are the ovaries, which, together with the uterus and the fallopian tubes, constitute the female reproductive tract. Ovaries functions: oogenesis and secretion of the female sex steroid hormones, progesterone and estrogen. ovary is attached to the uterus by ligaments The ovary has three zones. The cortex is the outer and largest zone. It is lined by germinal epithelium and contains all of the oocytes, each of which is enclosed in a follicle. The ovarian follicles are also responsible for steroid hormone synthesis. The medulla is the middle zone and is a mixture of cell types. The hilum is the inner zone, through which blood vessels and lymphatics pass. The ovarian steroid hormones have both paracrine and endocrine functions. The functional unit of the ovaries is the single ovarian follicle The functional unit of the ovaries is the single ovarian follicle, which comprises one germ cell surrounded by endocrine cells. When fully developed, the ovarian follicle serves several critical roles: It will provide nutrients for the developing oocyte; release the oocyte at the proper time (ovulation); prepare the vagina and fallopian tubes to aid in fertilization of the egg by a sperm; prepare the lining of the uterus for implantation of the fertilized egg; and, in the event of fertilization, maintain steroid hormone production for the fetus until the placenta can assume this role.  Oogenesis In the developing ovaries, primordial germ cells produce oogonia by mitotic divisions until gestational weeks 20–24. Beginning at gestational weeks 8–9, some of these oogonia enter the prophase of meiosis and become primary oocytes. The meiotic process continues until approximately 6 months after birth, at which point all oogonia have become oocytes. The oocytes remain in a state of suspended prophase; the first meiotic division will not be completed until ovulation occurs many years later. At birth, only 2 million oocytes remain; by puberty, only 400,000 oocytes remain; by menopause , few, if any, oocytes remain. females do not produce new oogonia Whereas males continuously produce spermatogonia and spermatocytes,  The development of ovarian follicles The development of ovarian follicles occurs in the following stages, which are illustrated in Figure 10.7: 1. First stage. The first stage of follicular development parallels prophase of the oocyte. Thus the first stage of the ovarian follicle lasts many years. The shortest duration for the first stage is approximately 13 years (the approximate age at first ovulation); the longest duration is 50 years (the approximate age at menopause). As the primary oocyte grows, the granulosa cells proliferate and nurture the oocyte with nutrients and steroid hormones. During this stage, the primordial follicle develops into a primary follicle, theca interna cells develop, and granulosa cells begin to secrete fluid. No follicle progresses beyond this first stage in prepubertal ovaries. 2. Second stage. This stage takes place over a period of 70–85 days and is present only during the reproductive period. During each menstrual cycle, a few follicles enter this sequence. A fluid containing steroid hormones, mucopolysaccharides, proteins, and FSH accumulates in a central area of the follicle called the antrum. The steroid hormones reach the antrum by direct secretion from granulosa cells. The granulosa and theca cells continue to grow. At the end of the second stage, the follicle is called a graafian follicle and has an average diameter of 2–5 mm.  3. Third stage. … , occurring 5–7 days after menses, A single graafian follicle achieves dominance over its cohorts, and the others regress. Within 48 hours, the dominant follicle grows to 20 mm in diameter. On day 14 of a 28-day menstrual cycle, ovulation occurs and the dominant follicle ruptures and releases its oocyte into the peritoneal cavity. At this time, the first meiotic division is completed and the resulting secondary oocyte enters the nearby fallopian tube, where it begins the second meiotic division. In the fallopian tube, if fertilization by a sperm occurs, the second meiotic division is completed, producing the haploid ovum with 23 chromosomes. The residual elements of the ruptured primary follicle form the corpus luteum. The corpus luteum is composed primarily of granulosa cells but also of theca cells, capillaries, and fibroblasts. The corpus luteum synthesizes and secretes steroid hormones,. If fertilization does occur, the corpus luteum will secrete steroid hormones until the placenta assumes this role, later in pregnancy. If fertilization does not occur, the corpus luteum regresses during the next 14 days ( and is replaced by a scar called the corpus albicans.  Synthesis and Secretion of Estrogen and Progesterone The ovarian steroid hormones, progesterone and 17β- estradiol, are synthesized by the ovarian follicles through the combined functions of the granulosa cells and the theca cells (Fig. 10.8). all steps discussed previously for the adrenal cortex and the testes.. In the ovaries, all steps in the biosynthetic pathway are present including aromatase, which converts testosterone to 17β-estradiol, the major ovarian estrogen. Progesterone and 17β-estradiol are synthesized as follows: Theca cells synthesize and secrete progesterone. Theca cells also synthesize androstenedione; this androstenedione diffuses from the theca cells to the nearby granulosa cells, which contain 17β- hydroxysteroid dehydrogenase and aromatase. In the granulosa cells, androstenedione is converted to testosterone and testosterone is then converted to 17β- estradiol. FSH and LH each have roles in the biosynthetic process. LH stimulates cholesterol desmolase in the theca cells, the first step in the pathway. FSH stimulates aromatase in the granulosa cells, the last step in the synthesis of 17β-estradiol. Regulation of the Ovaries controlled by the hypothalamic-pituitary axis the hypothalamic hormone is GnRH and the anterior pituitary hormones are FSH and LH. GnRH ovarian function in the female is driven by pulsatile activity of the hypothalamic-pituitary axis. GnRH is delivered directly to the anterior lobe of the pituitary in high concentration, where it stimulates pulsatile secretion of FSH and LH. FSH and LH then act on the ovaries to stimulate follicular development and ovulation and to stimulate the synthesis of the female sex steroid hormones. FSH and LH Every 28 days a sequence of follicular development, ovulation, and formation and degeneration of a corpus luteum is repeated in the menstrual cycle. The first 14 days of the menstrual cycle involve follicular development and are called the follicular phase. The last 14 days of the menstrual cycle are dominated by the corpus luteum and are called the luteal phase. The actions of FSH and LH on follicular development and on ovulation are explained as follows ♦ FSH. The granulosa cells are the only ovarian cells with FSH receptors. Initial actions of FSH stimulate the growth of granulosa cells in primary follicles and stimulate estradiol synthesis. The locally produced estradiol then supports the trophic effect of FSH on follicular cells. Thus the two effects of FSH on the granulosa cells are mutually reinforcing: more cells, more estradiol, ♦ LH. Ovulation is initiated by LH. Just prior to ovulation, the concentration of LH in blood rises sharply and induces rupture of the dominant follicle, releasing the oocyte. LH also stimulates formation of the corpus luteum, a process called luteinization, and maintains steroid hormone production by the corpus luteum during the luteal phase of the menstrual cycle.  Negative and Positive Feedback In females, the hypothalamic-pituitary axis is controlled by both negative and positive feedback, depending on the phase of the menstrual cycle (Fig. 10.9). ♦ In the follicular phase of the menstrual cycle, FSH and LH stimulate synthesis and secretion of estradiol by follicular cells. One action of estradiol is negative feedback on GnRH secretion by the hypothalamus and FSH and LH secretion by the anterior pituitary. ♦ At midcycle, the feedback pattern reverses. Estradiol levels rise sharply as a result of the proliferation of follicular cells and the stimulation of estradiol synthesis that occurred during the follicular phase. When a critical level of estradiol is reached , estradiol has a positive feedback effect on GnRH secretion by the hypothalamus ,causing further secretion of FSH and LH. This burst of hormone secretion by the anterior pituitary, called the ovulatory surge of FSH and LH, then triggers ovulation of the mature oocyte ♦ In the luteal phase of the menstrual cycle, the major hormonal secretion of the ovaries is progesterone.. One of the actions of progesterone is negative feedback on GnRH secretion by the hypothalamus and FSH and LH secretion by the anterior pituitary. ♦ Inhibin is produced by ovarian granulosa cells. As in the testes, it inhibits FSH secretion from the anterior pituitary. ♦ Activin is also produced by ovarian granulosa cells and stimulates FSH secretion.  Actions of Estrogen and TheProgesterone physiologic actions of estrogen and progesterone are summarized in Tables 10.2 and 10.3. In general, the two ovarian steroid hormones function in a coordinated fashion to support reproductive activity of the female including development of the ovum, development and maintenance of the corpus luteum to sustain a fertilized ovum, maintenance of pregnancy, and preparation of the breasts for lactation. Occasionally, they antagonize or modulate each other’s actions. Over the course of the menstrual cycle, estrogen secretion by the ovaries precedes progesterone secretion, preparing the target tissues to respond to progesterone. An example of this “preparation” is seen in the up-regulation of progesterone receptors by estrogen in several target tissues. Without estrogen and its up-regulatory action, progesterone has little biologic activity. Conversely, progesterone down-regulates estrogen receptors in some target tissues, decreasing their responsiveness to estrogen Actions of Estrogen and Progesterone on Development of the Female Reproductive Tract At puberty, the ovaries, driven by pulsatile secretion of FSH and LH, begin to secrete estrogen. estrogen promotes the growth and development of the female reproductive tract: the uterus, fallopian tubes, cervix, and vagina. Progesterone is also active in these tissues, usually increasing their secretory activity. Thus in the uterus, estrogen causes cell proliferation, cell growth, and increased contractility; progesterone increases secretory activity and decreases contractility. In the fallopian tubes, estrogen stimulates ciliary activity and contractility, aiding in the movement of sperm toward the uterus; progesterone increases secretory activity and decreases contractility. In the vagina, estrogen stimulates proliferation of epithelial cells; progesterone stimulates differentiation but inhibits proliferation of epithelial cells  Actions of Estrogen and Progesterone on Menstrual Cycle follicular phase Based on a “typical” 28-day cycle, the follicular phase of the menstrual cycle is the 14-day period preceding ovulation. This phase, which is also called the proliferative phase, is dominated by estrogen. 17β-Estradiol, whose secretion increases markedly during this phase, has significant effects on the endometrial lining of the uterus, preparing it for the possibility of accepting a fertilized ovum: Estradiol stimulate growth of the endometrium, growth of glands and stroma, and elongation of the spiral arteries, which supply the endometrium. causes the cervical mucus to become copious, watery, and elastic.  The luteal phase The luteal phase of a 28-day menstrual cycle is the 14-day period following ovulation. This phase also is called the secretory phase and is dominated by progesterone. Proliferation of the endometrium slows, and its thickness decreases. The uterine glands become more tortuous, accumulate glycogen in vacuoles, and increase their mucus secretions. The stroma of the endometrium becomes edematous. The spiral arteries elongate more and become coiled. Progesterone secretion decreases the quantity of cervical mucus, which then becomes thick Actions of Estrogen and Progesterone On Breasts Development of adult breasts is absolutely dependent on estrogen. The breasts, are composed of lobular ducts lined by a milk-secreting epithelium. Small ducts converge and empty into larger ducts that converge at the nipple. Estrogen also increases the amount of adipose tissue, giving the breasts their characteristic female shape. Progesterone collaborates with estrogen by stimulating secretory activity in the mammary ducts. In Pregnancy The highest levels of estrogen and progesterone occur during pregnancy, synthesized in early pregnancy by the corpus luteum and in mid-to-late pregnancy by the placenta. Estrogen stimulates growth of the myometrium, growth of the ductal system of the breasts, prolactin secretion, and enlargement of the external genitalia. Progesterone maintains the endometrial lining of the uterus and increases the uterine threshold to contractile stimuli, thus preserving the pregnancy until the fetus is ready to be delivered.. Other Actions of Estrogen and Progesterone estrogen contributes to the pubertal growth spurt, closure of the epiphyses at the end of the growth spurt, and the deposition of subcutaneous fat (i.e., female fat distribution). Progesterone has a mild thermogenic action, which increases basal body temperature during the luteal phase of the menstrual cycle. This increase in basal body temperature during the luteal phase.the increase in temperature can be used retrospectively to determine the time of ovulation Events of the Menstrual Cycle The menstrual cycle recurs approximately every 28 days over the reproductive period. The cycle length can vary from 21 to 35 days, but the average length is 28 days. The variability in cycle length is attributable to variability in the duration of the follicular phase; the luteal phase is constant. day 0 marks the onset of menses from the previous cycle. The hormonal changes and events of a 28-day menstrual cycle are illustrated in Figure 10.10. 1. Follicular or proliferative phase. 2. Ovulation. 3. Luteal or secretory phase 4. Menses  1. Follicular or proliferative phase. The follicular phase occurs from day 0 until day 14. During this period, a primordial follicle develops into a graafian follicle and neighboring follicles regress). the remaining follicle is called the dominant follicle. Early in the follicular phase, receptors for FSH and LH are up-regulated in ovarian theca and granulosa cells and the gonadotropins stimulate the synthesis of estradiol. The follicular phase is dominated by 17β-estradiol, whose levels steadily increase. cause proliferation of the endometrial lining of the uterus and inhibit GnRH secretion by the hypothalamus and FSH and LH secretion by the anterior pituitary by negative feedback (see Fig. 10.9). 2. Ovulation. Ovulation occurs on day 14 of a 28-day menstrual cycle. Regardless of cycle length, ovulation typically occurs 14 days prior to menses Ovulation follows a burst of estradiol secretion at the end of the follicular phase: The burst of estradiol has a positive feedback effect on GnRH secretion by the hypothalamus and FSH and LH secretion by the anterior pituitary (called the FSH and LH surge). The FSH and LH surge then causes ovulation of the mature ovum. At ovulation, cervical mucus increases in quantity and becomes watery. Estradiol levels decrease just after ovulation, but they will increase again during the luteal phase. 3. Luteal or secretory phase. The luteal phase occurs from days 14–28, ending with the onset of menses. During the luteal phase, the corpus luteum develops and begins synthesizing estradiol and progesterone. The high levels of progesterone stimulate secretory activity of the endometrium and increase its vascularity. in the follicular phase, estradiol causes the endometrial lining to proliferate; in the luteal phase, progesterone is preparing the endometrium to receive a fertilized ovum. Basal body temperature increases during the luteal phase because progesterone increases the hypothalamic temperature set point. The cervical mucus becomes less abundant and thicker, Late in the luteal phase, if fertilization has not occurred, the corpus luteum regresses. With this regression, the luteal source of estradiol and progesterone is lost, and blood levels of the hormones decrease abruptly. 4. Menses. Regression of the corpus luteum and the abrupt loss of estradiol and progesterone cause the endometrial lining and blood to be sloughed (menses or menstrual bleeding). Typically, menses lasts 4–5 days, corresponding to days 0 to 4 or 5 of the next menstrual cycle. During this time, primordial follicles for the next cycle are being recruited and are beginning to develop