Female Physiology PDF

Female Physiology Ovarian and Menstrual Cycle Overview of Interactions between Female Cycles 1. Follicle grows → more granulosa cells 2. Hence increase in release of oestrogen by these cells...

Female Physiology Ovarian and Menstrual Cycle Overview of Interactions between Female Cycles 1. Follicle grows → more granulosa cells 2. Hence increase in release of oestrogen by these cells 3. Oestrogen causes ○ proliferation of endometrium ○ Low conc → neg feedback on FSH/LH ○ High conc → pos feedback on FSH/LH 4. LH surge 5. Causes Ovulation (D14) 6. Leftover “follicle” becomes corpus luteum (lutein cells) 7. Which releases progesterone/oestrogen (increase) 8. Which induces secretory endometrium 9. If no pregnancy corpus luteum degenerates 10. Decrease on progesterone/oestrogen ○ No endometrial support → menstruation ○ No inhibition on FSH/LH → follicle growth again Ovarian and Menstrual Cycle Overview of Interactions between Female Cycles 1. Follicle grows → more granulosa cells 2. Hence increase in release of oestrogen by these cells 3. Oestrogen causes ○ proliferation of endometrium ○ Low conc → neg feedback on FSH/LH ○ High conc → pos feedback on FSH/LH 4. LH surge 5. Causes Ovulation (D14) 6. Leftover “follicle” becomes corpus luteum (lutein cells) 7. Which releases progesterone/oestrogen (increase) 8. Which induces secretory endometrium 9. If no pregnancy corpus luteum degenerates 10. Decrease on progesterone/oestrogen ○ No endometrial support → menstruation ○ No inhibition on FSH/LH → follicle growth again  Ovarian Cycle Series of changes in ovary during which follicle matures, ovum is shed, and corpus luteum develops Follicular phase (D1-14) for follicle growth, Luteal phase (D15-28) for corpus luteum activity Folliculogenesis May take >6 months for primordial follicle to grow and mature into an ovulatory follicle There is always presence of early antral and pre-antral follicles in the ovaries between puberty and menopause 1. Primordial follicle Single layer of squamous stromal cells (pre-granulosa cells) Present before birth Each month between puberty/menopause, some are recruited and activated via signals to form: 2. Primary follicle Cuboidal granulosa cells Formation of zona pellucida 3. Pre-antral (2˚ follicle) Proliferation to stratified epithelium Connective tissue outside granulosa cells form theca cells which function with granulosa cells to produce oestrogen: ○ LH → inner theca cells produce androgens ○ FSH → conversion to oestrogen via aromatase Folliculogenesis May take >6 months for primordial follicle to grow and mature into an ovulatory follicle There is always presence of early antral and pre-antral follicles in the ovaries between puberty and menopause 4. Early antral follicle Small antrums (fluid filled spaces) Follicular cells by oocyte forms cumulus oophorus At start of each menstrual cycle 10-25 pre-antral and early antral follicles develop into larger antral follicles, however only 1 dominant follicle will continue to develop (dependent on amount of local oestrogen within follicle) 5.. Antral follicle 1 single antrum 6. Mature/Graafian/3˚/preovulatory follicle 1˚ oocyte completes 1st mitotic division → 2˚ oocyte Cumulus oophorus separates and floats in antral fluid connected by corona radiata Folliculogenesis May take >6 months for primordial follicle to grow and mature into an ovulatory follicle There is always presence of early antral and pre-antral follicles in the ovaries between puberty and menopause 7. Ovulation LH major initiator Ballooning walls of follicle and ovary ruptures at sight where they are joined (stigma) → expelled into peritoneal cavity 8.. Corpus Luteum Luteal and thecal cells Forms fibrous clot Secretes progesterone/oestrogen (for 3M if pregnancy occurs) Degenerates after 10D if no pregnancy occurs to form: 9. Corpus albicans Mass of fibrous tissue Gradually resorbed in ovary Hormonal Control Normal Plasma Concentrations: Overall controlled by GnRH pulses released by hypothalamus Ovarian hormones: Oestrogen peaks middle of follicular and luteal stage (D12 + D21) Progesterone peaks (D21) Anterior pituitary hormones: LH and FSH rise toward end LH surge (D14) causes ovulation Hormonal Control of Cycles Follicular Phase GnRH released by hypothalamus → FSH/LH by anterior pituitary LH → Theca cells produce androgens FSH → pre-antral and early antral follicles continue development → enlargement and multiplication of granulosa cells → Converts androgens to oestrogens via aromatase Oestrogen and inhibin (granulosa cells) → negative feedback on LH/FSH Only dominant follicle survives drop in FSH Hormonal Control of Cycles Ovulation Follicle maturation → secretes large amounts of oestrogen which has positive feedback effect on hypothalamic pituitary axis LH surge causes ovulation: ○ Stimulates primary oocyte to complete first meiotic division → 2˚ oocyte ○ Increase in antrum size and blood flow ○ Release of enzymes and prostaglandins by granulosa cells → break down follicular ovarian membranes ○ Granulosa cells produce more progesterone and decrease production of oestrogen ○ Ruptured follicle → corpus luteum Hormonal Control of Cycles Luteal Phase Increase in progesterone and oestrogen by corpus luteum negatively feedbacks to LH/FSH Release of inhibin → dec FSH Declining gonadotrophin (LH/FSH) levels prevent development of additional follicles and LH surges Corpus luteum degrades within 2W → decrease plasma progesterone and oestrogen Hormonal Control of Cycles  Summary: Function of Ovarian Hormones Oestrogen Low inhibits FSH/LH, high → LH surge Produced by: ○ Follicle: LH works on theca → androgens. FSH on granulosa cells → oestrogen ○ Corpus luteum Thins cervical mucus Proliferative phase Promote progesterone receptor expression Progesterone: Produced by: ○ Corpus luteum Thickens cervical mucus Inhibit prostaglandin so no contraction Low fallopian tube motility Anti Mullerian Hormone (AMH): indicates follicle number/ovarian reserve (product of growing follicles) Dec with age, infertility  Uterine/Menstrual Cycle Series of cyclic changes that the uterine endometrium goes through each month in response to the waxing and waning of ovarian steroid hormones in the blood Phases of Menstrual Cycle: Menstrual phase (D1-5) Proliferative phase (D6-14) Secretory phase (D15-28) Endometrium (part of uterus shed) is made up of: Stratum functionalis - functional ○ Columnar epithelium ○ Connective tissue stroma ○ Simple tubular uterine glands ○ Spiral arteries Stratum basalis - unresponsive to ovarian hormones ○ Same cell types but more compact  Menstrual Phase (D1-5) Shedding of stratum functionalis of endometrium Average amount of blood lost = 30-40ml (up to 60ml) 1. Decrease in oestrogen/progesterone deprive endometrium of hormonal support 2. Increase in prostaglandin levels (produced by endometrium in response to decrease in oestrogen) → vasoconstriction of spiral arterioles → uterine contractions 3. Ischaemic endometrial cells die due to decrease in oxygen and nutrients 4. Spiral arterioles then dilate, resulting in haemorrhaging through weakened capillary walls 5. Stratum functionalis sloughs off Proliferative/ Preovulatory Phase (D6-14) Rebuilding of stratum functionalis (2-8mm) Proliferation of glandular epithelial cells, stroma and blood vessels with enlargement of glands Increase in plasma oestrogen (via dominant follicle development): ○ Promotes progesterone receptor expression on endometrial cells ○ Thins cervical mucus - allows passage of sperm into uterus for ovulation Ovulation marks end of proliferative phase Histo: Glands long-straight with absence of secretory products  Secretory / Postovulatory Phase (D15-18) Prepares endometrium for implantation Glands and stroma enlarge, arteries elongate Nutritious glycogen, mucopolysaccharides and glycoproteins secreted Driven by progesterone and oestrogen Rapid increase in progesterone causes: ○ Cervical mucus thickening - barrier to sperm and bacteria to protect embryo if fertilisation has occured ○ Inhibits prostaglandin-induced contractions of myometrium If fertilisation does not occur: Histo: Corpus luteum degenerates Sawtooth and coiled glands with secretory No production of progesterone → spasm of arteries, low products present oxygen levels → blood enters fragmented capillaries and Stroma abundant in blood vessels menses begins again Endometrium twice as thick