Female Reproductive Physiology and Menstrual cycle Lecture 4 Dr. Zahoor Dr. Shaikh Mujeeb Ahmed 1 Objectives • • • • Oogenesis and the stages of follicle development Ovulation and formation of corpusluteum Ovarian cycle Secretion of FSH and LH through negative and positive feedback mechanisms during a menstrual cycle • Uterine cycle • Draw a diagram and show changes in FSH, LH, estradiol, progesterone, and correlate these with ovarian and uterine changes during the menstrual cycle 2 Female Reproductive Physiology • Characterized by complex cycling • Ovaries – Primary female reproductive organs • Produce ova (oogenesis) • Secrete female sex hormones – Estrogen (estradiol) – progesterone 3 Female Sex Hormones –These are steroid hormone –Estrogen » Maturation and maintenance of entire female reproductive system . » Essential for ova maturation and release » Establishment of female secondary sexual characteristics » Essential for transport of sperm from vagina to fertilization site in oviduct » Contributes to breast development in anticipation of lactation –In general action of estrogen is important in preconception events 4 Female Sex Hormones –Progesterone » Important in preparing suitable environment for nourishing a developing embryo/fetus » Contributes to breasts’ ability to produce milk –In general progesterone is important in post conception events 5 OOGENESIS [GAMETOGENENSIS] • Formation of Primary oocytes from oogonium is completed before birth, 6-7 million oogonia by the fifth month of gestation. Soon Atresia starts and the number starts reducing. • After birth the number is reduced to 2 million (No new oocyte appear after birth ) • At puberty – 300, 000 -- oogonia present. • During reproductive age only 400-500 ova mature and ovulate . 6 Oogenesis 7 OOGENESIS [GAMETOGENENSIS] • The first meiotic division of primary oocyte begins during embryonic life but is arrested at prophase • Primary oocyte remains in the state of meiotic arrest for years and is completed only at ovulation [Release of ovum from ovary] at puberty. 8 • At ovulation it forms Secondary Oocyte which contains half the Chromosomes (22+x) and 1st polar body which undergoes degeneration. • The secondary oocyte then undergoes the 2nd meiotic division but is arrested at metaphase, and completed during fertilization. • It form the mature ovum (22+x) and the 2nd polar body. • The second polar body too undergoes degeneration 9 Oogenesis Spermatogenesis • Identical steps of chromosome replication and Accomplished within two months division during gamete production in both sexes – Timing and end result are very different Oogenesis Take anywhere from 12 to 50 years to complete on cyclic basis from onset of puberty until menopause Postpubertal male can produce several hundred million sperm each day Female born with limited, largely nonrenewable supply of germ cells Each primary spermatocyte yields four equally viable spermatozoa Each primary oocyte yields only one cytoplasm-rich ovum and three cytoplasm-poor polar bodies that disintegrate Female reproductive system • We will discuss 1. Ovarian cycle 2. Hormonal effects (hypothalamus & ant. Pituitary) 3. Uterine or menstrual cycle 11 1. Ovarian Cycle • • • • Average ovarian cycle lasts 28 days Normally interrupted only by pregnancy Finally terminated by menopause Ovarian cycle Consists of two alternating phases – Follicular phase(1-14 days ) • Dominated by presence of maturing follicles – Luteal phase(15-28 days) • Characterized by presence of corpus luteum 12 Ovarian Cycle-Follicular phase – Granulosa cells of some primary follicles proliferate – Theca cells proliferate (estrogen secreting cells) – Theca cells and Granulosa cells are collectively known as follicular cells – Under the effect of FSH 15-20 of the follicles grow rapidly forming secondary follicle which are capable of secreting estrogen – Oocyte inside each follicle enlarges 13 Ovarian Cycle-Follicular phase – One follicle usually grows more rapidly and mature (graafian follicle) about 14 days after onset of follicular development – Graafian follicle bulges on ovarian surface ruptures to release secondary oocyte from ovary (ovulation)- facilitated by burst in LH secretion – Released oocyte enters oviduct where it may or may not be fertilized 14 Development of the Follicle, Ovulation, and Formation and Degeneration of the Corpus Luteum 15 Ovarian Cycle-Luteal phase • Last 14 days of ovarian cycle – The remnants of the ruptured graafian follicle develop into Corpus luteum under influence of LH (leuteinization) – The granulosa cells are filled with yellowish lipid- lutein. – Becomes highly vascularized 16 Ovarian Cycle-Luteal phase – Corpus Luteum has endocrine functions and it secretes progesterone & estrogen (more of progesterone). It remains for 14 days (14- 28 days ). – If fertilization does not occurs degenerates into Corpus Albicans. it – If fertilization takes place it persists until placenta is formed & secrete increase quantity of progesterone & estrogen (corpus luteum of pregnancy) 17 Ovarian Cycle 18 2. EFFECT OF PITUITARY HORMONES ON OVARIAN CYCLE 19 Regulation of Ovarian Cycle by hormonal interactions 1. During follicular phase, rise in FSH signals ovarian follicle to secrete more estrogen 2. Rise in estrogen feeds back to inhibit FHS secretion which declines as follicular phase proceeds 3. LH rises in follicular phase • As it peaks in mid-cycle, it triggers ovulation 4. Estrogen output decreases and mature follicle is converted to a corpus luteum 20 Regulation of Ovarian Cycle by hormonal interactions 5. 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 6. FSH can start to rise again, initiating new cycle 21 Hormonal regulation of female sexual cycles Important keys about hypothalamo hypophysial ovarian axis • The master key is the hypothalamic factors which changes the rate of secretion of anterior pituitary • Pituitary hormones affects the rate of ovarian hormones secretion through the ovarian cycle. • Cyclic Changes in ovarian hormones produces cyclic changes in uterus (menstrual cycle), breast, and other secondary sex organs • As long as there is high level of estrogen (E) & progesterone (P), the endometrium is maintained without menstruation (as during pregnancy) • So, for menstruation to occur, there must be a period of high (E) & (P) (to thickness (prepare) the uterus followed by sudden (abrupt) in their levels as during: 1. Normal menstrual period 2. Intake of contraceptive pills (which contain high E & P; menstruation occurs only after stop of pills) Relationship between pituitary gonadotropins & ovarian hormones (E & P) • Usually –ve feedback mechanism (E & FSH) (P & LH) except when there is a very high estrogen levels (it becomes + ve feedback (at ovulation time) SO that: • At the end of previous cycle and start of new cycle, there in E & P plus inhibin hormones (caused by degeneration of corpus luteum (CL) and in FSH (w stimulate growth of new follicles) • After 5 days, the growing follicles will secrete estrogen that will inhibits FSH • At 12 days, estrogen is markedly increased, making +ve FB on pituitary caused marked increased in LH (LH surge) and FSH. Both will induce ovulation. • After ovulation (after day 14), the formed CL will secrete high amount of E & P (mainly progesterone) plus inhibin hormone (the 3 hormones are secreted from lutein cells) • E , P, & inhibin hormones from CL will inhibit FSH, LH then: a. If no fertilization occur, CL will degenerate (E & P) degeneration of endometrium; new menstrual cycle (note: menstrual cycle starts by menstruation) b. If fertilization occurs, CL will grow (CL of pregnancy) till 4th month when placenta is formed; both of them will maintain high E & p maintain endometrium and pregnancy 28 1 5 12 14 Follicular phase 26 28 1 26 28 1 26 28 1 Luteal phase FSH 28 1 5 12 14 Estrogen Ovulatory phase 28 1 5 12 5 12 5 12 14 Progesterone 28 1 28 1 14 26 28 1 LH 14 26 28 1 28 1 5 12 14 Follicular phase 26 28 1 Luteal phase FSH 28 1 1 5 12 14 26 28 Estrogen Ovulatory phase 28 1 5 12 5 12 5 12 14 26 28 1 26 28 1 Progesterone 28 1 28 1 14 LH 14 26 28 1 Production of estrogen by ovarian follicle 32 3. Uterine Cycle / Menstrual cycle • Reflects hormonal changes during ovarian cycle • Averages 28 days • Outward manifestation of cyclic changes in uterus is menstrual bleeding once during each cycle • Consists of three phases – Menstrual phase (3-5days) – Proliferative phase (6-14 days) – Secretory or progestational phase (15-28 days) 33 • Estrogen stimulates growth of both endometrium and myometrium . • It also induces synthesis of progesterone receptors in endometrium. • Progesterone: make endometrial connective tissue loose and edematous • Growth of endometrial blood vessels and glands to secrete glycogen 34 Uterine Cycle-Menstrual phase – 3-5 days of cycle – Characterized by discharge of blood and endometrial debris from vagina – First day of menstruation is considered start of new cycle – Coincides with end of ovarian luteal phase and onset of follicular phase 35 Uterine Cycle-Menstrual phase – As corpus luteum degenerates the level of progesterone & estrogen drops that results in Release of uterine prostaglandin • Causes vasoconstriction of endometrial vessels – Disrupts blood supply – Causes death of endometrium • Stimulates mild rhythmic contractions of uterine myometrium – Help expel blood and endometrial debris from uterine cavity out through vagina (menstrual flow) • Bleeding lasts for 3-5 days, 30-150 ml of blood is lost per cycle. Fibrinolysins are present which dissolves any clots. 36 Uterine Cycle • Proliferative phase (6-14days) – Begins concurrent with last portion of ovarian follicular phase • Endometrium starts to repair itself and proliferate under influence of estrogen from newly growing follicles • Glands and arteries proliferate and there is increases thickness of endometrium – Estrogen-dominant proliferative phase lasts from end of menstruation to ovulation – Peak estrogen levels trigger LH surge responsible for ovulation 37 Uterine Cycle Secretory or progestational phase(15-28day) – Uterus enters this phase after ovulation when new corpus luteum is formed – Corpus luteum secretes large amounts of progesterone and estrogen • Under effect of Progesterone – The endometrium grows further in thickness with increase in secretions of glands and arteries become more coiled – The secretion are rich in electrolytes, enzymes and glycogen which provide nourishment to the developing embryo before implantation, if fertilization has taken place. – If fertilization and implantation does not occur • Corpus luteum degenerates • New follicular phase and menstrual phase begin once again 38 Various factors can disrupt the menstrual cycle • Weight loss/low body weight • Disordered eating • Vigorous physical activity • Stress Athletic Menstrual Irregularities (AMI ) • • • • Amenorrhea ( Cessation of Menstrual periods) Oligomenorrhea (Less flow, irregular) Anovulatory cycle In general population menstrual cycle dysfunction occurs – 2-5% • But survey done in Athlete(Daily 3.5 hours of moderate intensity sports) showed Menstrual cycle irregularity 2-51% 40 AMI (C0NT) • MECHANISM RESPONSIBLE • Rapid loss of weight , decreased body fat, dietary insufficiencies. Stress, intensity of training, age at onset of training. • Hormonal changes responsible – FSH-LH environment totally unbalanced , – Decreased estrogen in follicular phase – Decreased progesterone in luteal phase IMPORTANT- All women athlete returned to normal within 6 months after training 41 42 THANK YOU 43