Menstrual cycle Flashcards
What is required to maintain the HPG axis
Pulsatile release of GnRH and gonadotrophins LH and FSH
This is important in feedback
Describe the length of the menstrual cycle
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
What does the 2 cell 2 gonadotrophin theory suggest?
LH receptors on theca and FSH receptors granulosa cells.
Progestrone and androstediol enzymes in theca
Oestradiol enzymes in the granulosa cells
Describe the stages of the menstrual cycle
refer to diagram on slide 7 for better understanding
- Late Luteal/Early follicular:
- The CL is dying, so there is reduced progesterone secretion and so there is reduced negative feedback. This allows for an interrise in FSH, which allows for recruitment of a cohort of follicles in the ovary. - Mid follicular:
Dominant follicle selection occurs and the follicle releases E2 which initially exerts negative feedback and reduces FSH levels. - Mid cycle:
When E2 exerts the threshold of >300pmol it exhibits positive feedback. This triggers the LH surge and induces ovulation - Mid luteal:
The corpus luteum releases high levels of progesterone that reinstates negative feedback and reduces LH and FSH secretion
Progesterone overcomes E2
In what species does the menstrual cycle occur in?
All mammals have cyclical ovarian function & the same reproductive system (in terms of HPG axis) to produce a mature egg and the necessary sex steroids
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
What is the Oestrus cycle?
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 fertilisation 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.
What are the breeding cycles in animals
Polyestrus: continuous breeders
seasonal polyestrous: 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.
Describe the HPO axis: hypothalamic/ pituitary/ ovarian (HPO) axis
The hypothalmus produces GnRH
The pituatary produces LH and FSH with positively feedback into the ovary.
The ovary produces oestrogen and progesterone that exert negative and positive feedback in the follicular phase. They feedback negatively to the pituitary and the hypothalamus in the luteal phase
- Activin and inhibin are produced by the ovary and can exert positive and negative feedback on the pituitary
What are the gonadal factors that regulate FSH secretion
Inhibin, Activin & Follistatin
*It was postulated for a long period that there are gonadal factors that regulate FSH secretion.
Activin: stimulates FSH secretion.
1986 – isolated Activins from follicular fluid which stimulate FSH secretion
Follastin: – binds activin with high affinity » neutralizes FSH-stimulating ability of activin
1987 – isolated another FSH-suppressing protein from follicular fluid called Follistatin.
What is the effect of Inhibin on FSH
Inhibin inhibits FSH secretion.
Study: Using ovariectomized (ovx) sheep, GnRH agonist was injected in the presence and absence of inhibin. (we use sheep because sheep are a better model – produce 2 lambs similar to humans )
Result: there was an absence of an FSH response to inhibin treated ewes
What are the subtypes for inhibin and activin?
Biosynthesis of inhibins and activins occurs from 3 genes, makes precursor protein:
TGFβ-superfamily of protein: The genes encode for larger precursor proteins which are then processed proteolytically.
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
No alpha chain in activin
At what stage are activins and Inhibins produced
In the early transition of follicles Activins predominate
Inhibin production increases as you move through folliculogenesis.
*Activins correlate with an increase in FSH
*Inhibins correlate with a decrease in FSH
study: Inject rats in the late antral phase with Inhibin anti-serum – what will anti-serum to Inhibin do? Bind it and prevent it from working – hence see an increase in FSH. However if inject with normal serum – there is no peak of FSH as you’d expect at this stage of MC.
(Late follicular phase corresponding with larger antral follicles)
How does AMH affect folliculogenesis
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
AMH may ‘fine tune’ follicle development by inhibiting early maturation of these follicles.
* May reduce follicle sensitivity to FSH, thereby inhibiting aromatase mRNA expression and activity. The effects on cell proliferation are uncertain, but it does not clearly have the apoptotic effect seen in the Müllerian duct during differentiation.
AMHR2 has been detected in theca (blue layer) from a range of follicle sizes, but its actions are unknown. As the follicles develop and grow, AMH levels decline, but the causative factor/s remains to be discovered. The decrease in AMH then releases the inhibitory effect, allowing these larger follicles to become responsive to FSH, and stimulating aromatase and oestradiol production.
If too many follicles are recruite this may lead to early menopause
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.
1980s: found to be expressed in rodent ovaries
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?
Describe folliculogeneisis mentioning gonadotropins with Inhibin and activin
When the follicles are growing, when you have follicles that are at the right size and stage to respond to that increase in FSH, they are recruited into the menstrual cycle to cintinue grow.
FSH drives this growth, the follicles are producing oestrogen, activins are increasing. These will reinforce FSH and drive follicle growth.
The follicles start to produce alot more oestrogen and inhibins. As the ratio of activins to inhibins alters, as oestradiol levels increase. Oestrogen will act on the hypothalmus and pituatary. This is going to lead to a fall in FSH. The follicles will die off. Any other follicles that have reached the right size will die off except the dominant follicle
Describe Follicle Selection
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
How does the dominant follicle survive the fall in FSH?
-As FSH falls, LH increases.
Dominant follicle acquires LH receptors on granulosa cells.
Other follicles do not, so they loose their stimulant and die.
