Menstrual Cycle 1

The length of a menstrual cycle is the number of days between the first day of menstrual bleeding of one cycle to the onset of menses of the next cycle Median duration of MC is 28 days with most cycles between 25=30 days Menstruation lasts 3-8 days, written as 7/28 or 5-6/27-32 MC<21 days=polymenorrheic; MC>35 days=oligomenorrheic Menstrual cycle typically most irregular around extremes of reproductive life i.e menarche and menopause

Theca cell: cholesterol, pregnenolone, DHEA Granulosa cell: Androstenedione, oestradiol corpus luteum: progesterone

Early follicular- progesterone down; FSH up Mid follicular-oestrogen increases, FSH falls Mid cycle- Lh surge Mid luteal - high progesterone, low LH and FSH

Menstrual cycles occur only in humans, primates (apes and monkeys) & is named for the regular appearance of menses i.e. shedding of then endometrial lining Oestrus cycle in animals named because of: The cyclic appearance of behavioural sexual activity (heat or oestrus) They do not menstruate – the endometrium is reabsorbed if fertilization does not occur Day 0 of the oestrous cycle is the day of beginning of sexual receptivity Ovulation usually occurs early in cycle as high oestrogen levels stimulate sexual behaviour as well as exerting positive feedback Different species have different lengths of cycles Some are poly-oestrous i.e. go into heat several times/year (cats, cows, pigs); others are di-oestrous (twice/year) and some have only one breeding season/year i.e. mono-estrous (eg. Bears, foxes, wolves) and usually in spring Rabbits have no oestrous cycles and are induced to ovulate by mating and can conceive at any arbitrary moment.

Seasonal polyoestrus: These animals only cycle during a determined season, in response to specific environmental cues, such as an increase or decrease of light hours. Short day breeders such as the ewe, nanny and doe, start cycling as the days get shorter in the fall. Long day breeders, on the other hand, are animals such as the mare that start cycling as the days are getting longer in the spring Monoestrus: These are animals which have only one cycle per year.In this category we find the wolf, and the fox. Polyoestrus: The animal can cycle during the entire year, independently of environmental cues.

1985 purified Inhibin → produced by testis (Sertoli cells) and ovary (Granulosa cells) Disulphide-linked protein dimers Common α-subunit with different β-subunits giving two forms of Inhibin Both forms specifically suppress FSH secretion by pituitary without affecting LH secretion 1986 – isolated Activins from follicular fluid which stimulate FSH secretion 1987 – isolated another FSH-suppressing protein from follicular fluid called Follistatin – binds activin with high affinity » neutralizes FSH-stimulating ability of activing

Biosynthesis of inhibins and activins occurs from 3 genes, makes precursor protein: α- protein, specific for Inhibin βA- protein, can form either Activin/Inhibin βB- protein, can form either Activin/Inhibin Inhibins take 2 forms depending on β-chain composition Inhibin A and Inhibin B Activins take 3 forms depending on β-chain composition Activin A (βA-homodimer), Activin B (βB-homodimer) & Activin AB (βAβB-heterodimer)

AMH is a glycoprotein and also a member of the TGFβ superfamily In males expressed from week 8 of development causes regression of the Müllerian ducts by a wave of apoptosis. In 1980s found to be expressed in rodent ovaries Over the last decade a new and interesting role for AMH has emerged in the ovary It is expressed by ovarian granulosa cells with levels peaking in selectable follicles (large preantral and small antral follicles) » then decreasing AMH production in preantral follicles is variable, but has been detected from the primary stage onwards – species variation?

AMH has 2 windows of action on folliculogenesis Inhibits transition from primordial to primary follicles Inhibits FSH-dependent cyclical recruitment of follicles by inhibiting FSH-stimulated aromatase and FSH receptor expression → in the normal cycle would act to prevent over-recruitment of growing follicles

Raised FSH present a “window” of opportunity FSH threshold hypothesis One follicle from the group of antral follicles in ovary is just at the right stage at the right time…. This becomes the dominant follicle which survives fall in FSH and goes onto ovulate Known as “selection” Can be in either ovary Oestradiol levels rise reinstating negative feedback at pituitary causing FSH levels to fall prevents further follicle growth

As FSH falls, LH increases. Dominant follicle acquires LH receptors on granulosa cells. Other follicles do not, so they loose their stimulant and die.