Physiology of Female Reproductive System and Menstrual Cycle PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Physiology of Reproductive Glands: The Female Reproductive System Module Endocrine and Breast Lecturer Brona Murphy - [email protected] Ebrahim Rajab – [email protected]  LEARNING OUTCOMES 1....

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Physiology of Reproductive Glands: The Female Reproductive System Module Endocrine and Breast Lecturer Brona Murphy - [email protected] Ebrahim Rajab – [email protected]  LEARNING OUTCOMES 1. Describe the physiological functions of the female reproductive system with particular emphasis on the gonads 2. Describe the factors that control female gonad function 3. Describe the hormonal changes that occur during the menstrual cycle 4. Describe the uterine changes that occur during the menstrual cycle 5. Outline menopause  INTRODUCTION: REPRODUCTION Depends on union of male and female gametes to form new individual Male and female reproductive systems designed to enable union of genetic material – Includes gonads, reproductive tract and accessory sex glands Female reproductive system also houses and nourishes the offspring until (s)he can survive independently FEMALE REPRODUCTIVE FUNCTIONS Functions – Production of ova (oogenesis) – Reception of sperm – Transport of sperm and ovum to common site for union (fertilization or conception) Product of fertilization is known as an embryo After first two months of intrauterine development, embryo is known as a fetus – Maintenance of the developing fetus until it can survive in the outside world (gestation or pregnancy) Formation of placenta (exchange organ between mother and fetus) – Giving birth to the baby (parturition) – Nourishing infant after birth by milk production (lactation) FEMALE REPRODUCTIVE ORGANS The female reproductive organs can be divided into the upper genital tract – ovaries, fallopian tubes, uterus and cervix and the lower genital tract – the vagina and vulva (or pudendum refers to external genitals of FIG. 5.2 The pelvis and perineum contain and support female) terminal parts of the gastrointestinal, urinary, and reproductive systems. (A) In women The upper genital organs and the Source: Gray's Anatomy for Students, Fifth Edition. vagina are located in the pelvis, while Drake, Richard L. Chapter 5: Pelvis and Perineum the vulva is a part of the perineum. These organs participate in several hormonal and mechanical pathways that are responsible for secondary sexual development and reproduction FEMALE REPRODUCTIVE ORGANS Two ovaries, two oviducts, uterus, cervix, vagina, clitoris Ovaries – The primary female reproductive organs/gonads, – consist of two ovaries in the female. – They perform the dual function of 1. producing gametes (gametogenesis) – ova (eggs) 2. secreting sex hormones – estrogen & progesterone Organs – 2 ovaries – oocytes (immature egg): produce sex hormones – 2 oviducts – conduct oocyte from ovary to uterus – Uterus – chamber for developing fetus, endometrial lining – Cervix – opening of uterus; secretes mucus that facilitates sperm – Vagina – organ of sexual intercourse; birth canal – Clitoris – sex organ responsive to stimulation  FEMALE REPRODUCTIVE ORGANS Oviducts (uterine or Fallopian tubes) – In close association with ovaries – Pick up ova on ovulation – Serve as most common site for fertilization – conduct oocyte from ovary to uterus Uterus – Responsible for maintenance of fetus during development – Responsible for expelling fetus at end of pregnancy – Site of menstruation Cervix (lower portion of uterus) – Contains single, small opening pathway for sperm to enter uterus; FIG. 5.54 Uterus. Anterior view. The Secretes a clear alkaline fluid to anterior halves of the uterus and vagina facilitate the passage of sperm have been cut away passageway for delivery of baby from uterus Source: Gray's Anatomy for Students, Allows menstrual blood to flow Fifth Edition. Drake, Richard L. Chapter from uterus to vagina 4: Urogenital System  FEMALE REPRODUCTIVE ORGANS Vagina – Muscular, expandable tube that connects uterus to external environment – Passageway for menstrual blood – Receives ejaculate during copulation – Serves as a conduit for childbirth. – Vaginal opening located in perineal region between urethral opening and anal opening Partially covered by thin mucous membrane, hymen (typically disrupted by first sexual intercourse; following this, irregular remnants of the hymen fringe the vaginal opening.) FIG. 5.2 The pelvis and perineum contain and support terminal parts of the gastrointestinal, urinary, and reproductive systems. (A) In women FIG. 5.74 Superficial Features of the Perineum in Women. (A) Overview. (B) Close-up of external genitalia. Source: Gray's Anatomy for Students, Fifth Edition. Drake, Richard L. Chapter 5: Pelvis and Perineum FEMALE REPRODUCTIVE ORGANS Vulva – Collective term for female external genitalia - the labia majora, the labia minora, the clitoris – Labia minora and labia majora Skin folds that surround vaginal and urethral openings – Clitoris Small erotic structure located at anterior end of folds of labia minora FIG. 5.74 Superficial Features of the Perineum in Women. (A) Overview. (B) Close-up of external genitalia. Source: Gray's Anatomy for Students, Fifth Edition. Drake, Richard L. Chapter 5: Pelvis and Perineum  OOGENESIS - Spermatogenesis Oogenesis INTRODUCTION Accomplished within Take anywhere from 12 two months to 50 years to complete Sexual reproduction requires the on cyclic basis from production of specialised haploid onset of puberty until cells (called gametes) through the menopause process of meiosis Post-pubertal male can Female born with – Leads to development of mature produce several limited, largely spermatozoa in the male hundred million sperm nonrenewable supply of (spermatogenesis) each day germ cells – Leads to development of mature ova Each primary Each primary oocyte in the female (oogenesis) spermatocyte yields yields only one four equally viable cytoplasm-rich ovum spermatozoa and three cytoplasm- The steps of chromosome poor polar bodies that replication and division during disintegrate gamete production are identical in both sexes, however, – Timing and end result are very different  OOGENESIS Defined as the development of an immature oocyte into a secondary oocyte or mature ovum (if fertilization occurs). Begins in utero during fetal growth and ends with menopause. At birth, a normal ovary contains about 1–2 million primary oocytes. There is a continuous decline in the number of primary oocytes after birth. OOGENESIS Female germ cells develop in the embryonic yolk sac & participate in the development of the ovary. The germ cells, called oogonia, actually divide by mitosis. Oogonia undergo mitosis only during the prenatal period. During the last part of fetal life, the oogonia begin the early steps of the first meiotic division but do not complete it. – Known now as primary oocytes The primary oocytes remain in this state of meiotic arrest for years until they are prepared for ovulation.  OOGENESIS Before birth, each primary oocyte is surrounded by a single layer of connective tissue-derived granulosa Fig. 44.15 (Modified from White BA, cells. Together, an oocyte and Porterfield SP. Endocrine Physiology. 4th ed. Philadelphia: Mosby; 2013.) surrounding granulosa cells make up a primary follicle. At birth only about 2 million primary follicles remain, each containing a single primary oocyte capable of producing a single ovum. No new oocytes or follicles appear after FIG. 10.43 Follicular development. birth, with the follicles already present in (A) Primary follicles in the ovarian the ovaries at birth serving as a cortex. O1, primary oocyte; TF, thecal cells; ZG, granulosa cells; reservoir from which all ova throughout ZP, zona pellucida. From Young B, the reproductive life of a female must Woodford P, O'Dowd G, et al. 2013 Wheater's functional histology: a arise. text and colour atlas, 6th edn. Churchill Livingstone, Philadelphia. OOGENESIS - Just before ovulation primary oocyte completes its first meiotic division to produce ▪ 2 daughter cells (each with 23 chromosomes) ▪ Secondary oocyte & polar body - Secondary oocyte is ovulated & fertilized ▪ Sperm entry triggers second meiotic division ▪ Secondary oocytes that are not fertilized never complete this final division - During second meiotic division one half set of 23 chromosomes (maternal chromosomes) unite with 23 paternal chromosomes in the mature ovum to complete fertilization  MENSTRUAL CYCLE From puberty until menopause a portion of follicles develop on a cyclic basis In females, during the reproductive years, regular cyclical changes occur in the ovaries (ovarian cycle) and related changes occur in the uterus (uterine cycle). These cycles are known as the menstrual cycles. The cycle duration varies from 23 to 35 days with an average duration of 28 days.  MENSTRUAL CYCLE AND HORMONAL CONTROL Hypothalamus – pituitary axis Hypothalamus: Gonadotropin- releasing hormone (GnRH) Pituitary: Follicle stimulating hormone (FSH) and Luteinizing hormone (LH) OVARIAN CYCLE CONSISTS OF ALTERNATING FOLLICULAR AND LUTEAL PHASES - After puberty ovary constantly alternates between two phases - Follicular phase (days 1-14 approx.) - Dominated by presence of maturing follicles - Produce a mature egg for ovulation - Luteal phase - Characterized by presence of corpus luteum - Prepare female reproductive tract for pregnancy in case fertilization of released egg occurs - Cycle interrupted only if pregnancy occurs or is terminated by menopause  OVARIAN CYCLE – FOLLICULAR PHASE Pool of primary follicles gives rise to developing follicles – Only follicles that respond to FSH stimulation are “recruited” at beginning of follicular phase – Typically, 15-20 follicles are recruited – As follicle grows estrogen is produced in increasing quantities One of the follicles, “dominant” follicle, grows more rapidly than others, developing into a mature follicle FIG. 10.45 Stages of follicular development in the ovary. (Graafian follicle) within about 14 days after the onset Source: Medical Sciences. Jeanette Naish. of follicular development – Rupture of the follicle is facilitated by a burst in LH secretion – Ovum (secondary oocyte) quickly drawn into oviduct where fertilization may take place – Rupture of follicle signals end of follicular phase FIG. 10.46 The menstrual cycle. (A) Changes in the endometrium during the menstrual cycle. (B) Stages of follicular development during the menstrual cycle. (C) Hormonal changes during the menstrual cycle; the peak in oestradiol immediately precedes ovulation. (D) At ovulation a woman's basal temperature increases by around half a degree and remains high throughout the luteal phase. Source: Medical Sciences. Jeanette Naish OVARIAN CYCLE – LUTEAL PHASE Ruptured follicle changes rapidly and forms corpus luteum – Function is to secrete abundant quantities of progesterone and smaller amounts of estrogen – estrogen secretion in follicular phase & progesterone secretion in luteal phase is essential for preparing uterus for implantation of fertilized ovum FIG. 10.45 Stages of follicular development in the ovary. Source: Medical Sciences. Jeanette Naish. If released ovum is not fertilized or does not implant, then the corpus luteum degenerates within about 14 days leading to formation of the corpus albicans One ovarian cycle is now complete FIG. 10.46 The menstrual cycle. (A) Changes in the endometrium during the menstrual cycle. (B) Stages of follicular development during the menstrual cycle. (C) Hormonal changes during the menstrual cycle; the peak in oestradiol immediately precedes ovulation. (D) At ovulation a woman's basal temperature increases by around half a degree and remains high throughout the luteal phase. Source: Medical Sciences. Jeanette Naish PHASES OF OVARIAN CYCLE Follicular phase: from day 1 to day 14 approx. – Day 1: Several follicles begin to develop – Day 6 approx: One follicle begins to develop more rapidly than others. Others regress forming atretic follicles – Developing follicle secretes estradiol (estrogen) FIG. 10.45 Stages of follicular development in the ovary. Source: Medical Sciences. Jeanette Naish. – Day 14 approx.: The mature follicle (Graafian follicle) ruptures (ovulation). Ovum is expelled PHASES OF OVARIAN CYCLE Luteal phase: from day 14 to day 28 approx. Ruptured follicle develops into corpus luteum Corpus luteum secretes estradiol and progesterone If ovum released at ovulation is not fertilized, corpus luteum has preset lifespan of approx.10 days. FIG. 10.45 Stages of follicular development in the ovary. Source: Medical Sciences. Jeanette Naish. It then regresses to the corpus albicans. Next cycle begins. OVARIAN CYCLE REGULATED BY COMPLEX HORMONAL INTERACTIONS During follicular phase, rise in FSH signals ovarian follicle to secrete more estrogen – Rise in estrogen feeds back to inhibit FSH secretion which declines as follicular phase proceeds Near end of follicular phase, there is a dramatic rise in circulating estrogen. – When estrogens rise above a certain level, they no longer inhibit release of LH and FSH. Instead, they stimulate release of both. LH peaks in mid-cycle and triggers ovulation During luteal phase, estrogen output decreases and mature follicle is converted to a corpus luteum Corpus luteum secretes progesterone and estrogen during luteal phase Progesterone output inhibits release of FSH and LH Low LH – corpus luteum degenerates Progesterone levels decline FSH can start to rise again, initiating new cycle  UTERINE CYCLE The fluctuations in circulating levels of hormones during the ovarian cycle give rise to the uterine cycle. Because it reflects hormonal changes during the ovarian cycle, the uterine cycle averages 28 days, as does the ovarian cycle, although even normal adults vary considerably from this mean. The outward manifestation of the cyclic changes in the uterus is the menstrual bleeding once during each cycle. The uterine cycle consists of three phases: 1. Menstrual phase 2. Proliferative phase 3. Secretory/progestational phase.  THE MENSTRUAL PHASE The menstrual phase is the most overt phase, characterized by discharge of blood and endometrial debris from the vagina. By convention, the first day of menstruation is considered the start of a new cycle. – It coincides with the end of the ovarian luteal phase & onset of a new follicular phase. Menstruation typically lasts for 5 - 7 days after degeneration of the corpus luteum, coinciding in time with the early portion of the ovarian follicular phase The drop in progesterone & estrogen secretion removes inhibitory influences from the hypothalamus and anterior pituitary – FSH and LH secretion increases & a new follicular phase begins. After 5 - 7 days under the influence of FSH and LH, the newly growing follicles are secreting enough estrogen to induce repair and growth of the endometrium. THE PROLIFERATIVE PHASE & SECRETORY (PROGESTATIONAL) PHASE The proliferative phase of the uterine cycle begins concurrent with the last portion of the ovarian follicular phase as the endometrium starts to repair itself and proliferate under the influence of estrogen from the newly growing follicles. After ovulation, when a new corpus luteum is formed the uterus enters the secretory, or progestational, phase, which coincides in time with the ovarian luteal phase. The corpus luteum secretes large amounts of progesterone and estrogen which prepare the uterus to support an early embryo. If fertilization and implantation do not occur, the corpus luteum degenerates and a new follicular phase and menstrual phase begin once again. MENSTRUAL CYCLE Follicular Phase Luteal Phase  PUBERTAL CHANGES IN FEMALES Female reproductive system remains quiescent until puberty GnRH stimulates the anterior pituitary gonadotropic hormones These stimulate estrogen secretion by activated ovaries LH – Growth and maturation of female reproductive tract – Development of female secondary sexual characteristics Fat deposition in breast, buttocks, thighs FIG. 8.9 Relative serum luteinizing hormone (LH) and follicle- stimulating hormone (FSH) levels across the life span in women. Redrawn from Braunwald E, et al: Harrison’s Principles of Internal Medicine, 4th ed., New York, 1987, McGraw-Hill. MENOPAUSE - Unique to females - Refers to the cessation of menstrual cycles in middle age (45-55) - Menopause occurring before the age of 40 is considered premature. - Diagnosed after 12 months of amenorrhea - Traditionally been attributed to the limited supply of ovarian follicles present at birth. - Recent evidence suggests, however, that a midlife hypothalamic change instead of aging ovaries may trigger the onset of menopause. – Specifically, a change in hypothalamic pituitary sensitivity to estrogen feedback in perimenopausal women. - Evolutionarily, menopause may have developed as a mechanism that prevented pregnancy in women beyond the time that they could likely rear a child before their own death. MENOPAUSE Preceded by period of progressive ovarian failure – Increasingly irregular cycles – Dwindling estrogen and progesterone levels perimenopause Ovarian estrogen production declines from as much as 300 mg per day to essentially nothing. – Adipose tissue, adrenal cortex and liver continue to produce small amounts of oestrogen (~ 20 mg/day) – Loss of estrogen primarily affects skeleton and cardiovascular system  MULTIPLE CHOICE QUESTIONS 1. A surge of FSH and LH is induced in the adenohypophysis 24hours before ovulation and the first meiotic division of the primary oocyte resumes. At what stage does the oocyte become arrested until it becomes fertilized? A. First meiotic division, prophase B. First meiotic division, metaphase C. Second meiotic division, prophase D. Second meiotic division, metaphase E. Second meiotic division, anaphase Answer is D 2. As menstruation ends estrogen levels in the blood rise rapidly. What is the source of the estrogen? A. Anterior pituitary gland B. Corpus luteum C. Developing follicles D. Endometrium E. Stromal cells of the ovaries Answer is B 3. Traditionally, which of the following is attributed to be the cause of the menopause? A. Midlife change in hypothalamic pituitary sensitivity to estrogen feedback B. Reduced levels of gonadotropic hormones secreted from the anterior pituitary gland C. Reduced responsiveness of the follicles to the stimulatory effects of gonadotropic hormones D. Reduced rate of secretion of progesterone from the corpus luteum E. Reduced numbers of follicles available in the ovary for stimulation by gonadotropic hormones Answer is E  Recommended Reading Medical Sciences. Jeannette Naish. Chapter 10. Endocrinology and the Reproductive System. Or, Endocrine and Reproductive Physiology. Bruce White, John Harrison, Lisa Mehlmann. Chapter 8. Life Cycle of the Male and Female Reproductive Systems. Or, Master Medicine: Physiology. J McGeown. Chapter 8. Endocrine physiology.