Female Reproductive Cycles

Control of Ovulation and the Corpus Luteum

• The female reproductive cycle is divided into two phases:

  • Follicular phase:

  • Last wave of follicles growing contains the dominant follicle to be ovulated.

  • Dominated by secretion of estrogen and FSH (Follicle-Stimulating Hormone).

  • Precedes ovulation.

  • Luteal phase:

  • Follows ovulation.

  • Dominated by the corpus luteum (CL) secreting progesterone.

Follicular Growth and Regression During the Luteal Phase

• Using ultrasonography, defined follicular growth and regression during the luteal phase in cows and mares.

• In cattle:

  • Dominant Antral Follicles:

  • Several develop sequentially during the cycle.

  • Follicle Waves:

  • Cycles or waves within an estrual cycle are delimited by the onset of growth of the next wave.

  • First Dominant Follicle:

  • Regresses around mid-luteal phase.

  • Second Dominant Follicle:

  • Begins growth immediately after the first one regresses.

  • Third Follicle Wave:

  • Develops if the second wave is regressing at CL regression.

  • Ovulatory Follicle:

  • Selected as the dominant follicle still in the developmental stage when CL regression initiates.

Gonadotropin Release During the Luteal Phase

• Final growth phase of follicle development can be initiated during the luteal phase:

• Influenced by a slow pulse rate of gonadotropin release due to higher progesterone secretion from the CL.

• Rapidly growing follicles require exposure to a faster gonadotropin (LH) pulse rate, which occurs at the onset of CL regression.

• At the time of increasing LH, there is a passive rise in the pulsatile release of gonadotropins.

  • Progesterone (P4) Levels: Indicated by the orange line.

  • FSH Levels: Indicated by the blue line.

Dominant Follicle Maintenance

• The dominant follicle maintains its status by producing substances that inhibit development of other antral follicles.

• Inhibin:

  • A peptide hormone produced by granulosa cells.

  • Inhibits secretion of FSH.

• The dominant follicle compensates for low FSH concentration with a higher number of FSH receptors compared to competitor follicles.

• Continuing growth of follicles depends on the gonadotropin environment:

  • Improper gonadotropin exposure leads to atresia (regression) almost immediately.

  • Follicular Atresia:

  • Involves invasion by inflammatory cells and replacement of connective tissue with an ovarian scar.

Role of Estrogen and Ovulation

• Estrogen:

  • Stimulates growth and development of granulosa cells in the dominant antral pre-ovulatory follicle.

  • Signals hypothalamus and anterior pituitary about readiness for ovulation.

• Pre-ovulatory LH Surge:

  • Begins approximately 24 hours before ovulation in most domestic species (cows, dogs, goats, pigs, sheep).

• Ovulation Process:

  • Rupture of the follicle accompanies resumption of meiosis I, with LH blocking meiosis-inhibitory factor (MIF).

  • Resumption of meiosis results in formation of the first polar body, completed before ovulation.

Induced Ovulators

• Some animals are considered induced ovulators (e.g. cats, rabbits, ferrets, minks, camels, llamas, alpacas):

  • Require copulation for ovulation to occur.

  • Copulation substitutes estrogens as the trigger for gonadotropin release.

  • Still need exposure to elevated estrogen concentrations before responding to copulation.

Luteinization Process and Follicle Rupture

• The LH surge affects granulosa cells allowing luteinization:

  • Transforms cells from estrogen-secreting to progesterone-secreting.

  • Takes place before ovulation.

  • As LH surge occurs, estrogen secretion declines alongside the onset of progesterone secretion.

• Additional effects from LH surge:

  • Secretion of relaxin and prostaglandin F2α from granulosa cells.

  • Affects connective tissue continuity of the thecal layers of the follicle facilitating follicle rupture and expulsion of the oocyte.

Main Functions of the Corpus Luteum

• The primary function of the CL is progesterone secretion:

  • Prepares uterus for initiation and maintenance of pregnancy (in case of fertilization).

• Formation of the CL occurs from the collapsed and folded wall of the follicle after ovulation.

• Following follicle rupture is hemorrhage into the follicular cavity that contains granulosa and theca cells along with a vascular system supporting cell growth and differentiation.

• In most domestic species, significant progesterone production by the CL begins within 24 hours of ovulation:

  • LH maintains the CL through a slow pulsatile secretion pattern (one pulse every 2-3 hours).

• In rodents and sheep, prolactin is the primary luteotropin maintaining the CL.

Effects of Copulation on Corpus Luteum

• In rodent species:

  • Luteal phase of the ovarian cycle extends due to copulation.

  • CL life span is only 1-2 days in the absence of copulation.

  • Copulation initiates prolactin release, prolonging luteal activity for up to 10 or 11 days without pregnancy.

  • This phenomenon is termed pseudopregnancy.

Corpus Luteum Lifespan

• The CL life span post-ovulation must be sufficient for a developing conceptus (embryos) to synthesize and release factors that permit CL maintenance.

• However, the lifespan must be relatively short to allow non-pregnant animals to return to a fertile state.

• In large domestic animals, the lifespan of the CL is approximately 14 days.

• For large domestic animals (e.g., cattle, goats, horses, pigs, sheep), the regression of the CL is controlled by uterine secretions: prostaglandin (PGF)2α.

• In contrast, in cats, dogs, and primates, CL regression is not controlled by PGF2α.

• Mode of Transfer of PGF2α:

  • Occurs from the uterus to the ovary via localized countercurrent transfer or general systemic transfer.

  • Local Countercurrent Transfer:

  • Movement of molecules from higher concentrations in the utero-ovarian vein to lower concentrations in the ovarian artery.