Reproductive physiology

• The SRY gene is the sex-determining region of the y-chromosome and regulates other genes
• testosterone (leydig cell) controls the development of the wolffian duct into accessory structures and the development of male external genitalia (via DHT)
• anti-mullerian hormones control the regression of the mullerian duct
• Determination of genetic sex:

  1. SRY gene produces testis determining SRY-protein
  2. this initiates the production of proteins causing medulla to differentiate into a testis
  3. which has a leydig cell (secretes testosterone) and a sertoli cell (secretes anti-mullerian hormone)
• Newly formed testes secrete:

  1. testosterone = internal genitalia associated with testes
  2. mullerian inhibiting substance (anti-mullerian hormone) = causes mullerian duct to degenerate
  3. dihydrotestosterone (DHT) = external genitalia associated with testes
• Female sex determination after bipotential stage:

  1. gonad cortex becomes ovary with SRY gene absence
  2. absence of testosterone causes wolffian duct to degenerate
  3. absence of anti-mullerian hormone allows mullerian duct to become the fallopian tube, uterus, and upper part of the vagina
• Male sex determination after bipotential stage:

  1. SRY gene directs medulla of the bipotential gonad to develop into testis
  2. anti-mullerian hormone from testis causes the mullerian duct to degenerate
  3. testosterone from testis converts wolffian duct into seminal vesicle, vas deferns, and epididymis (DHT controls prostate development)
• Analogous female and male genitalia:

  labia majora = scrotum

  labia minora = penis shaft

  clitoris = glans penis
• If a male lacks DHT then the male gonads will be present, the male internal genitalia will remain, and the male will develop female external genitalia
• Gonadotropin-releasing hormone (GnRH) controls the release of FSH and LH from the anterior pituitary gland and is pulsatile
• Gonads secrete sex steroids and inhibin (inhibits FSH)
• Functions of testis include sperm production from spermatid (spermatogenesis) and the production and secretion of testosterone
• Spermatogenesis (in seminiferous tubules):

  1. spermatogenia (stem cell) = mitosis
  2. primary spermatocyte = first meiosis
  3. secondary spermatocyte = second meiosis
  4. spermatids differentiate = spermatogenesis
  5. spermatozoa (lumen)
• The basal compartment is the space inside seminiferous tubules but external to sertoli cells and contains spermatogonia which eventually become spermatozoa
• adluminal compartment is the space inside seminiferous tubules including lumen and sertoli cells and contains spermatocytes, round spermatids, and newly formed immotile spermatozoa
• the blood-testis barrier separates devloping sperm from the immune system
• Sertoli (sustentacular) cells:

  • promote and sustain sperm development
  • secrete growth factors
  • secrete androgen-binding protein (allows increase of luminal testosterone concentration)
  • blood-testis barrier
  • phagocytosis of defective sperm
  • produce and secrete hormones
  • inhibin, MIS
• Leydig cells:

  • produce and secrete testosterone
  • active in fetal life (gonadogenesis)
  • quiescent after birth
  • active at puberty and on = sexual maturity and function
• In response to FSH and testosterone, sertoli cells support spermatogenesis
• in response to LH, leydig cells produce steroids, including testosterone
• FSH stimulates sertoli cells to secrete ABP and release paracrine agents
• increase in testosterone causes inhibition of LH and gNRH (which then causes FSH inhibition) and increases estrogen and DHT production
• The long-loop feedback action by the ovaries on the hypothalamic-pituitary acis is inhibitory (negative) and stimulatory (positive)
• Gonadotropin production follows the ovarian cycle, causing LH and FSH to increase during ovulation (day 14)
• When estrogen is high the positive feedback loop is activated to give rise to ovulation
• Follicle-stimulating hormone (FSH) in females:

  • stimulate growth of granulosa cell (converts testosterone into estrogen)
  • stimulates key enzyme aromatase
  • induces LH receptors on granulosa cell
• Lutenizing hormone (LH) in females:

  • stimulates growth of thecal cell (makes testosterone)
  • neutralizes action of peptide oocyte maturation inhibitor
  • induces pseudoinflammatory response by activating prostaglandin endoperoxide synthase
  • stimulates progesterone synthesis
• FSH injection will cause ovary to increase aromatase expression and stimulate oocyte maturation
• ovarian uterine cycle:

  1. follicular phase = progressive growth of ovarian follicles and causes one dominant follicle to bud out of the ovarian surface (menses to proliferative phase)
  2. ovulation = dominant follicle bursts and oocyte is released into abdominal cavity (increase in estrogen)
  3. luteal phase = most cells that were formed in follicle will stay in ovary and become the corpus luteum (degenerates without fertilization) (increase in progesterone and secretory phase)
• 1. GnRH levels effect ovary cycle
  2. this gives rise to ovarian hormone levels
  3. determines uterine cycle
• Ovarian and uterine cycle feedbacks:

  1. negative:
  2. decrease in steroid hormone level
  3. secretion of GnRH and gonadotropins
  4. growth of follicle (increase in estrogen)
  5. decrease in FSH
  6. dominant follicle outgrowth (critically high estrogen levels)
  7. positive:
  8. LH surge
  9. LH stimulates corpus luteum
  10. negative:
  11. increase in progesterone and estrogen
  12. LH drops
  13. corpus luteum regression
  14. corpus albicans
• Feedback effects summary:

  • low concentrations of estrogen inhibits FSH/LH production
  • inhibin inhibits FSH secretion
  • high concentrations of estrogen has positive feedback to stimulate LH secretion and some FSH (in response to GnRH)
  • increase in progesterone and estrogen concentrations causes feedback inhibition of GnRH (thus FSH/LH)