Male and Female Reproductive Physiology PDF

Male and female reproductive physiology 1  Intended learning outcomes Reproductive endocrinology - male & female reproductive physiology Overview: Introduction to reproductive endocrinology. Revisit the hypothalamic-pituitary-gonad axis from Lecture 1 & 2 in mor...

Male and female reproductive physiology 1  Intended learning outcomes Reproductive endocrinology - male & female reproductive physiology Overview: Introduction to reproductive endocrinology. Revisit the hypothalamic-pituitary-gonad axis from Lecture 1 & 2 in more detail. Male reproductive anatomy. Spermatogenesis and the role of sertoli and leydig cells. Endocrine control of spermatogenesis. The ovarian cycle, follicular development and the corpus luteum. The uterine cycle and the endometrium. The complex endocrine control of the menstrual cycle. After the lecture and personal study, students should be able to: Understand how gender and sex are determined Understand the major events in the foetal development of the genitalia Recall male and female reproductive anatomy Explain the physiology of reproductive function in the male and female Know the effects of testosterone Understand the process of spermatogenesis Know the roles and control of the testes Know the events of male puberty Know the effects of the major “female” hormones in the female reproductive system Understand the physiology and endocrinology of the ovarian and menstrual cycle Know the events of female puberty Know the events of menopause Determining Gender  Boy or girl? Development of the reproductive tracts (internal genitalia) All early embryos have 2 primitive duct systems, the Wolffian and Mullerian ducts with potential to form male or female tracts: In males Wolffian ducts è repro tract Mullerian ducts degenerate In females Wolffian ducts degenerate Mullerian ducts è repro tract Development into male or female depends upon hormones secreted by foetal testes – Testosterone (stimulated by human chorionic gonadotrophin (hCG) from placenta) and Mullerian inhibiting factor (MIF; induces regression of Mullerian ducts) Without stimulus of male testicular hormones, Wolffian ducts regress, Mullerian ducts develop & foetus will develop female characteristics After wk 6 DHT No testosterone, female phenotype Fig. 20-4, p. 746 DHT stimulates Fig. 20-5, p. 748  The Male Reproductive System  Urinary bladder Ureter Seminal vesicle Prostate gland Bulbourethral gland Ejaculatory duct Ductus deferens Penis Epididymis Testis Glans Urethra 8 penis  Essential reproductive function 1. Production of sperm (spermatogenesis) 2. Delivery of sperm to female How are these goals achieved? Testes Produce sperm and testosterone Scrotum Sac of skin in which testes are suspended Accessory glands (Seminal vesicles, prostate gland, bulbourethral gland) Secrete semen to suspend and sustain sperm Penis To transfer sperm to female Route of sperm Testes è epididymis è vas deferens è ejaculatory duct è urethra 9  The control of testicular function GnRH released from hypothalamus in bursts every 2-3 hrs Stimulates cells in anterior pituitary to secrete LH & FSH also in short bursts Bursts of GnRH release begin at 8-12 years (initially at night) to initiate puberty Frequency of bursts increases until levels of GnRH, LH, FSH & testosterone are same as in adult Rising levels of testosterone produce 2ndry sexual features Negative feedback control of FSH & LH by testosterone & inhibin 10  Testes Dual function: Producing sperm and secreting testosterone ~80% of testicular mass consists of highly coiled seminiferous tubules Leydig (interstitial) cells lie in connective tissue between seminiferous tubules In utero, testes develop in abdominal cavity of foetus Drop into scrotal sac before birth Sometimes descend more slowly – before puberty Cryptorchidism – individual has reached adulthood and testes have not descended Why is it important that testes descend? Lower temp outside body to facilitate spermatogenesis Nervous reflexes trigger muscle movement in scrotal sac to lower/raise testes according to external temp 11 Structure of the Testes  Testosterone Produced in Leydig cells Steroid hormone, derived from cholesterol Secreted into blood or into seminiferous tubules for sperm production Secretion stimulated at puberty & continues for life 13  1 Effects on events before birth Masculinises the reproductive tract and external genitalia Promotes descent of the testes into the scrotum (after birth testosterone production virtually ceases until puberty) 2 Effects on sex-specific tissues § Leydig cells secrete testosterone again at puberty § Promotes growth and maturation of repro system at puberty (10-14 years old) § Causes testes to enlarge and become capable of spermatogenesis § Maintains repro tract throughout adulthood 14  3 Other reproductive effects Develops libido at puberty and can maintain it for life Controls gonadotrophin hormone secretion (negative feedback - controls spermatogenesis) 4 Effects on secondary sexual characteristics § Induces characteristic male pattern of hair growth (beard, chest etc.) § Enlarges larynx & thickens vocal cords è Deep voice § Thickens skin § Causes male body shape § Eunuch – male castrated before puberty 15  5 Nonreproductive events Anabolic - promotes protein and bone growth / development èMales more muscular than females èGrowth spurt at puberty èCloses epiphyseal plates (Aromatase) Induces oil secretion by sebaceous glands è acne Aggressive behaviour (?) 16  Puberty Androgen secretion (e.g. dehydroepiandrosterone, DHEA) from the adrenal cortex (about 5% of total androgens) Testicular enlargement & pubic hair growth Trigger for not certain – programmed within adrenal cortex independent of ACTH? Testes mature and produce androgens and sperm triggered by FSH & LH (due to GnRH release) Exact trigger for GnRH release not clear pre-programmed? Critical body weight? Inhibition of melatonin secretion? 17  Puberty 2º sexual characteristics appear (caused by testosterone and metabolites) Growth of larynx Deepening of voice Increased bone mass Increased mass and strength of skeletal muscle Thickened skin Increased and thickened hair on trunk, arms, legs, face Somatic growth Induced by gonadal sex steroids, growth hormone and insulin-like growth factor Puberty lasts many years e.g. Facial hair pattern may not mature until 20-25 years of age 18 Spermatogenesis and its control  Spermatogenesis Conversion of germ cells (spermatogonia) into motile sperm Sperm produced in seminiferous tubules in testes 2 types of cells: Germ cells (in various stages of development) Sertoli cells – support spermatogenesis 20  Lumen of seminiferous tubule Spermatozoon differentiation takes 64 days Sertoli cell Spermatids Secondary spermatocyte Primary spermatocyte Tight junction Spermatogonium 21  Stages of spermatogenesis A) Mitotic proliferation – Spermatogonia (46 chromosomes) divide - one daughter cell remains undifferentiated, the other divides twice more to form primary spermatocytes (46 chromosomes) B) Meiotic division – 1st meiotic division - each primary spermatocyte divides into 2 haploid (23 double-stranded chromosomes) secondary spermatocytes 2nd meiotic division – secondary spermatocytes divide to form 2 single - stranded spermatids Testosterone required for mitosis and meiosis stages 22  Stages of spermatogenesis C) Spermiogenesis (Packaging) – spermatids converted to spermatozoa– removal of unnecessary cellular components and rebuilding into specialised, motile spermatozoa Follicle stimulating hormone (FSH) required for this process 23 Fig. 20-8, p. 753  Structure of Sperm Tail provides motility Acrosome (microtubules) Nucleus contains contains genetic material enzymes for penetration of centriole ovum Mitochondria 25 provide energy  Sertoli cells Form a blood-testes barrier Tight junctions protect the sperm from antibody attack Provides a regulated fluid composition which allows later stages of development of sperm – v. different from blood Provide nutrients for the developing cells Phagocytosis Remove surplus cytoplasm from packaging process & destroy defective cells Secrete seminiferous tubule fluid Used to carry cells to epididymis along pressure gradient Secrete androgen binding protein Binds testosterone so concentration remains high in lumen – essential for sperm production Secrete inhibin - hormone which regulates FSH secretion (negative feedback) and controls spermatogenesis During fetal development, secrete Müllerian-inhibiting factor (MIF) 26  Control of the testes Controlled by 2 gonadotropic hormones secreted by anterior pituitary Luteinizing hormone (LH) a.k.a.interstitial cell-stimulating hormone (ICSH) Acts on Leydig cells - regulates testosterone secretion Follicle stimulating hormone (FSH) Acts on Sertoli cells to enhance spermatogenesis – essential for spermatid re-modeling Secretion of LH and FSH is stimulated by gonadotropin-releasing hormone (GnRH) 27 Fig. 20-10, p. 755  The Female Reproductive System  Ovarian vessels Oviduct Endometrium Ovary Fimbriae Myometrium Uterus Cervical canal Cervix Vagina  Oviduct Ovary Vertebral column Fimbriae Uterus Cervix Urinary Rectum bladder Pubic bone Vagina Urethra Clitoris Labium Anus minora Labium majora  Essential reproductive function More complex roles than male - Production of ova Reception of sperm Transport of sperm & ova to site of fertilization Gestation Parturition Nourishment of the infant by lactation  How are these goals achieved? Ovaries Maturation & release of ova Oviducts (fallopian tubes) Site of fertilization Uterus Maintains foetus during gestation Expels foetus at end of gestation Cervix Has small opening to allow sperm thro’ to uterus Expands greatly during birth Vagina Receptacle for sperm Birth canal - uterus to outside Vaginal opening Allows penis in / baby out External genitalia (labia minor, major & clitoris) known as vulva No physiological involvement in repro (tho’ involved in stimulation)  Oogenesis Identical meiotic and mitotic divisions to male sperm production – but Oogenesis takes many years to complete Begins in utero Suspended for many years Begins again at puberty Completed at fertilization Oogenesis ceases at the menopause Stages Oogonium Mitotic proliferation prior to birth Chromosomes in each cell Arrested in first Primary meiotic division 46 oocytes At birth, ~ 2million primary follicles Increase in Enlarged nutrient rich After puberty, one primary oocyte reaches maturity and primary oocyte 46 is ovulated cytoplasm (First meiotic division completed just Oocyte loses half prior to ovulation) chromosomes but keeps First Secondary cytoplasm oocyte 23 polar body Meiosis Fertilization triggers 2nd Second polar body Mature meiotic division ovum 46 (23 from Polar bodies sperm, 23 degenerate from ovum)  Puberty Adrenarche 6-8 years of age (adrenal gland secretes androgens (e.g.DHEA) – similar to male puberty) Trigger not known – pre-programmed? Androgens eventually cause growth spurt Pubic hair growth starts Thelarce Breast development starts Menarche (onset of menstrual cycle) 10 – 16 years old ↑FSH & LH from pituitary (triggered by GnRH –cf males) ovaries producing steroids establishment of oestrogen inducing ovulation by positive feedback onset related to critical level of body fat – triggers GnRH release  Puberty 2º sexual characteristics induced by ovarian oestrogens Pubic hair Growth / maturation of repro tract (including uterus) and external genitalia Fat deposition – breasts, buttocks, thighs Closure of epiphseal plates (stops growing) cf testosterone in males Somatic growth Begins 2 years earlier in girls cf boys Induced by gonadal sex steroids, growth hormone and insulin-like growth factor (as for males)  Menopause – “oestrogen withdrawal syndrome” v Occurs typically in 5th decade of life as ovaries atrophy § Initial decrease in fertility, shortening of menstrual cycle § FSH levels rise - ovarian oestrogen, progesterone & inhibin fall § Cessation of ovulation and menstruation § Hot flushes (hypothalamic vasodilation & raised temp?), insomnia, § Vaginal & uterine atrophy, decreased breast size (oestrogen dependent tissues) § Longer term susceptibility to osteoporosis (oestrogen normally reduces effect of PTH) and cardiovascular disease (oestrogen normally reduces endothelin production?) The Ovarian Cycle  Ovarian cycle Lasts for 28 days (average) Has 2 phases: Follicular phase 1st half of cycle Maturation of egg, ready for ovulation at midcycle – ovulation signals end of follicular phase Luteal phase 2nd half of cycle Development of corpus luteum (yellow body) Induces preparation of reproductive tract for pregnancy (if fertilisation occurs)  The follicular Phase Primary follicle vBefore birth, the primary oocyte is surrounded by a single layer of granulosa cells vThis structure is called a primary follicle vThere are approx 2 million 1º follicles at birth vEach is capable of producing a single ovum vUntil puberty all 1º follicles degenerate to scar tissue (atresia) at some stage before ovulation vAfter puberty, 2º follicles develop cyclically Secondary follicle vOocyte grows (x1000) and follicle expands & becomes differentiated under hormonal influence vAfter puberty about 400 will be ovulated, the rest (99.98%) will undergo atresia vFollicular phase ends with ovulation  The Luteal Phase vFollicular cells left behind after ovulation undergo luteinisation – transformation to the corpus luteum vCorpus luteum secretes progesterone and oestrogen Oestrogen secreted in follicular phase and progesterone secreted in luteal phase essential for preparation of uterine lining for implantation vAfter ovulation, corpus luteum grows for 8-9 days vIf no fertilisation has occurred, it will survive no longer than 14 days after ovulation Corpus albicans is formed (White body – fibrous tissue) vDegeneration of corpus luteum signals start of new follicular phase vIf fertilisation has occurred, corpus luteum persists and produces increasing quantities of progesterone and oestrogen until after pregnancy The follicle, ovulation, corpus luteum Hormonal control of ovarian and menstrual cycles Hormonal control of the uterine and ovarian cycles (1/2) 5 2 8 6 6 3 Hormonal control of the uterine and ovarian cycles 7 3 4 7 1 4 1 Menstruation marks the beginning of both uterine & ovarian cycles. 2 A few days before menstruation, the anterior pituitary begins to increase secretion of FSH & LH 3 The follicles begin to mature and increase production of estrogen 4 The one follicle left secretes increasing amounts of estrogen, stimulating the uterus to grow During the first 12 days of the ovarian cycle, Estrogen exerts negative feedback on gonadotropin release. Then, on days 12-14, estrogen exerts positive feedback on the pituitary 5 As a result there is a surge in release of LH (& FSH, to a lesser extent) 6 LH surge triggers ovulation AND stimulates the follicle cells to develop into the corpus luteum and to secrete progesterone and estrogen. 7 Estrogen and progesterone are crucial for i) the maintenance of the uterine lining AND ii) send negative feedback to the anterior pituitary to inhibit gonadotropin release. 8 If the egg is not fertilised: The corpus luteum degenerates on day 26 of the cycle. 1 Without progesterone, the uterine lining sloughs off and menstruation occurs. 2 The decrease in estrogen and progesterone relieves the negative feedback on the anterior pituitary: GnRH, FSH & LH all ↑ The next round of follicles develop and the ovarian cycle restarts Fig. 20-18, p. 771 Feedback control of FSH and tonic LH secretion during the follicular phase Fig. 20-20, p. 773 Control of the LH surge at ovulation Fig. 20-21, p. 774