Reproduction 4

• Female reproductive system has primary sex organs/gonads (ovaries), accessory (secondary) sex organs (oviducts, uterus and vagina), and external genitalia (clitoris and vulva)

  
• Reproductive cycles

  • Menstrual cycles (some primates)
  • Estrous cycle (domestic mammals)

  
• Tonic center or pulse generator


  Located in the mediobasal hypothalamus, secretes GnRH in a pulsatile manner, responds to negative feedback effects of steroids
• Cyclic center or surge generator

  Located in the anterior hypothalamus, preoptic area, responds to positive feedback effects of estradiol
• Increasing concentrations of estradiol

  Anterior pituitary more responsive to GnRH, triggers an increase in GnRH pulse frequencies and amplitudes from the surge generator

  
• Steroids exert negative feedback effects

  At the level of the anterior pituitary - progesterone directly inhibits LH & FSH secretion, at the level of the hypothalamus - progesterone causes a decrease in GnRH pulse frequencies, estrogen causes a decrease in GnRH pulse amplitude and frequency
• Oogenesis

  1. Multiplication phase (primordial germ cells become oogonia, oogonial cells undergo proliferation by repeated mitotic divisions)

  2. Growth phase (pre-vitellogenesis growth period, vitellogenesis growth period)

  3. Maturation phase (accompanied by meiotic division, secondary oocyte and polar body formation)

  
• Oocyte size

  • Amphibians: 50 µm young, 1000-2000 µm mature
  • Birds: 40,000 µm
  • Mammals: 200 µm
• Folliculogenesis

  1. Gonadotropin-independent phase (primordial to secondary follicles)

  2. Gonadotropin-dependent phase (secondary to tertiary follicles)

  3. Recruitment (high FSH + low LH + no inhibin + no E2)

  4. Selection (low FSH + moderate LH + low inhibin)

  5. Dominance (low FSH + high LH + high inhibin)

  
• Cows have 2-3 follicular waves in every cycle but these follicles cannot ovulate until P4 decreases and E2 increases
• Follicle development

  • Small, dormant primary oocyte surrounded by single layer of squamous epithelial (follicular) cells and a basement membrane (basement lamina)
  • Larger primary oocyte surrounded by single layer of simple cuboidal epithelium (granulosa) cells and a basement membrane (basement lamina), FSH receptors induced on the granulosa cells by activin
  • Secondary (pre-antral) follicle - granulosa cells avascular, gap junctions, zona pellucida, theca formation, angiogenesis
  • Tertiary follicle - formation of lacunae, lacunae coalesce to form the antrum, continued angiogenesis in theca
  • Late tertiary/mature/Graafian follicle - eccentric primary oocyte, encircled by the corona radiata, cumulus oophorous, antrum containing fluid, theca interna and theca externa

  
• FSH induces LH receptors on granulosa cells


  Rising LH, prior to the surge, reduces FSH receptors on the same cells
• Inhibin, Activin and Follistatin

  Synthesized by granulosa cells in response to FSH, Inhibin inhibits FSH secretion, Activin stimulates FSH release, Follistatin inhibits FSH secretion (by binding to activin)
• Ovulation

  Extrusion of secondary oocyte + corona radiata + follicular fluid, rupturing of the Graafian follicle can occur at any point on the ovarian surface, mares - ovulation fossa

  
• Loss of granulosa cell to cell contacts, disruption of gap junctions during ovulation
• Antrum


  • Containing fluid
• Theca interna

  • Endocrine cells
• Theca externa

  • Myoid type cells and fibroblasts

  
• FOLLICULOGENESIS CONT'D

  1. FSH induces LH receptors on granulosa cells

  2. Rising LH, prior to the surge, reduces FSH receptors on the same cells

  3. ~ 12 hours prior to ovulation, the primary oocyte becomes the secondary oocyte – except dogs and foxes

  4. Follicle now ready for ovulation

  
• Inhibin

  Inhibits FSH secretion
• Activin

  Stimulates FSH release
• Follistatin

  Inhibits FSH secretion (by binding to activing)
• OVULATION

  1. Extrusion of secondary oocyte + corona radiata + follicular fluid

  2. Rupturing of the Graafian follicle can occur at any point on the ovarian surface

  3. Mares – ovulation fossa

  
• OVULATION CONT'D

  1. Increased follicular permeability

  2. Loss of granulosa cell to cell contacts

  3. Disruption of gap junctions

  4. Oocyte and corona radiata released

  5. Increased follicular pressure and follicular contractions

  6. Area of stigma stretches until it breaks

  7. Release of oocyte and follicular fluid
• Ovulators

  • Spontaneous ovulators (most domesticated animals)
  • Reflex (induced) ovulators (cat, rabbit, ferret, mink, camel family)
• OVULATION CONT'D

  1. Require coitus as a stimulus for normal ovulation

  2. In the absence of coitus, the Graafian follicle undergoes atresia

  
• Absence of coitus

  • No ovulation
  • Absence of corpora lutea
  • No luteal phases – only a follicular phase
• CL formation

  1. Migration of the thecal cells into the follicular cavity

  2. Differentiation of granulosa and thecal cells into luteal (lutein) cells

  3. Establishment of extensive vascular network
• OVULATION CONT'D

  1. Ovulation results in ruptured blood vessels in theca interna blood clot in the follicular cavity -> corpus hemorrhagicum

  2. Plasmin dissolves blood clot & mediates thecal cell migration

  3. Thecal cells develop into small luteal cells (theca-lutein cells); proliferate; characterized by the presence of lipid droplets and by the absence of cytoplasmic secretory granules

  4. Granulosa cells differentiate into large luteal cells (granulosa-lutein cells); hypertrophy; characterized by the presence of secretory granules that contain oxytocin, inhibin and relaxin and by the absence of lipid droplets

  5. Basement membrane is disrupted

  6. Angiogenic factors promote the vascularization of the CL

  7. Blood vessels invade interior of CL
• Progesterone

  • Prepares the reproductive tract for the initiation and maintenance of pregnancy
  • Estrogen priming required for effects of progesterone – induces expression of progesterone receptors
  • Progesterone down-regulates estrogen receptors
  • Primes hypothalamus for expression of estradiol-induced estrous behaviours

  
• Luteolysis

  1. Functional regression – stops progesterone synthesis and secretion – rapid effect

  2. Morphological (structural) regression – luteal cells degenerate slowly, leaving a connective tissue scar –corpus albicans
• Uterine PGF2 initiates CL regression

  1. Increased CL invasion by lymphocytes, eosinophils and macrophages

  2. Decreased blood flow to the CL

  3. Cessation of steroidogenesis

  4. Morphological changes in luteal cells

  
• Menstrual cycle

  • Blood flow
  • Premenstrual phase: The endometrium continues to mature until a sudden drop in hormone levels triggers menstruation
  • Menstrual phase: The surface of the endometrium sheds off resulting in menses
  • Proliferative phase (Follicular Phase): Endometrial cells proliferate and the lining thickens
  • Secretory phase (Luteal Phase): An egg is expelled from the ovary (ovulation)

  
• Estrous cycle


  • No blood flow
  • Proestrus, estrus, metestrus and diestrus
• Proestrus

  1. Follicle enlarges

  2. Estrogen increases

  3. Vascularity of the female reproductive tract increases

  4. Endometrial glands begin to grow

  5. Estrogen levels peak

  
• Estrus

  1. Sexual receptivity

  2. Estrogen decreases

  3. LH surge occurs

  4. Ovulation 24-48 hr after surge of LH

  5. Uterine motility high with contractions moving toward oviduct

  6. Sperm transport is optimal

  7. Cervical mucus volume increase

  
• Metestrus

  1. Estrogen low

  2. Corpus hemorrhagicum present

  3. Ovulation in cow

  4. Uterus: Contractions subside, Endometrial glands continue to grow, FSH increases, triggering growth of follicles

  
• Diestrus

  1. Progesterone high

  2. FSH low but increases at some point to cause growth of pre-ovulatory follicle

  3. Uterus: Secrets fluid but the volume of fluid decreases over time, Contraction stops, Corpus luteum regresses at the end of this period if female is not pregnant

  
• Estrous cycle types

  • Polyestrous animals – several cycles per year
  • Seasonal breeders – several cycles during certain parts of the year
  • Monoestrous animals – 1 estrous cycle per year
• Photoperiod and seasonal breeding

  1. Long-day breeders cycle when days get longer (spring) and are in anestrus in fall and winter

  2. Short-day breeders cycle when the length of daylight shortens (fall) and are in anestrus in spring and summer