Menstrual Cycle I Flashcards
What are the 6 aims of the MC? (6)
- selection of single haploid
-regular spontaneous ovulation
-correct number of chromosomes in egg
-Cyclical changes in the vagina, cervix and fallopian tube - Preparation of the uterus
- Support of the fertilised dividing egg
What is the key requirement to maintain the HPO axis? (2)
-pulsatile GnRH
- regular/ pulsatile gonadotrophins
The normal menstrual cycle (5)
- The length of a menstrual cycle = number of days b/w 1st day of menstrual bleeding of one cycle to the onset of menses of the next cycle
- Median duration of cycle =28 days with most cycles b/w 25-30 days
*Menstruation lasts 3-8 days, written as 7/28 or 5-6/27-32
*MC<21 days=polymenorrheic; MC>35days=oligomenorrheic
*Menstrual cycle typically most irregular around extremes of reproductive life i.e menarche and menopause
Menstrual cycle day/phase diagrams (7)
images
LL: dec. p+e2
EF: dec. p+e2, inc. FSH+LH surge -> intracycle rise of FSH (recruits early antral follicles) (MENSES)
MF: inc. e2 (inc. oestrogen- granulosa cells release from follicles), steady p(-tive feedback from oestreogen = dec. FSH)
LF: peaks of all
EL: drops
ML: highs for p+e2 (from CL, gran,+ theca)
LL: restart
Which steroids are made where? (2 cell gonadotrophin theory) (3)
Theca: predom. all the enzymes responsible for formation of progesterone family and androgen family (due to LH receptors)
Granulosa: androgens converted to oestrogen because aromatase only present here (FSH receptors)
Corpus Luteum: mixture of both
What are the roles of FSH? (5)
-cyclical recruitment of FSH
-GC multiplication
-Stimulation of E2 - leading to prolif of endometrium
-DF selection
-Introduction of LH receptors
What are the roles of LH? (3)
-Completion of Meiosis I in oocyte and start of meiosis II
-Ovulation
-CL formation w/ accompanying progesterone production
The menstrual cycle mini diagrams (4)
LL/EF: prog declines (CL dies if no pregn) = selectively raises FSH = intercycle rise
MF: E2 rises (-ve feedback) = FSH falls
Mid cycle: 2 days of E2 (>300pmol = +ve feedback- length of time +threshold) = LH Surge
ML: high prog = -tive feedback = low LH/FSH, P overcomes E2
Oestrus vs menstrual cycle (wider reading) - (7)
Menstrual cycles occur only in humans, primates and snakes for the regular appearance of menses I.e. shedding
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 (=poly babies)
* 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
Types of breeding cycles in animals (5)
Polyestrus: The animal can cycle during the entire year, independently of environmental cues. (e.g. primates, rat, sow, cow)
Monoestrus: These are animals which have only one cycle per year. (e.g. wolf and fox.
Seasonsal 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 start cycling as the days get shorter in the fall (e.g. ewe, nanny and doe)
-Long day breeders start cycling as the days are getting longer in the spring (e.g. mare)
HPO
Image
Inhibin (4)
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 (INHIBIT) FSH secretion by pituitary w/o affecting LH secretion
Activins - 1986
1986 – isolated Activins from follicular fluid which stimulate (ACTIVATE) FSH secretion
Follistatin -1987
1987- Follistatin – binds to activin with high affinity » neutralises FSH-stimulating ability of activins (suppressed FSH indirectly, by preventing stim.)
How do we know that Inhibins act selectively on FSH? - ovx sheep study (3)
Experiment using ovx sheep: GnRH agonist (activating) injected in the presence and absence of Inhibin
ovx= control + avoid intrinsic control of hormones
sheep = mono-ovulatory (like us)
= complete absence of FSH in inhibin induced sheep (no change in LH), compared to normal sheep
Images
Inhibin and activist subtypes (3)
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)
Inhibin: Inhibits FSH sec. =
-InhibinA- alpha and BetaA subunits
-InhibinB- alpha and BetaB subunits
Activin: stimulates FSH sec. =
-ActivinA- BetaA and BetaA subunits
-ActivinAB- BetaA and BetaB subunits
-ActivinB- BetaB and BetaB subunits
Follicle stage and production of inhibin and Activin - rat study proof (4)
image
-Granulosa cells produce diff. amounts of each, going through the menstrual cycle.
-Activins: high FSH in EFP correlation
-Inhibins: low FSH in LFP correlation
used rats - used rabbit serum and antiserum (checking what happens when you block inhibin) = raised FSH con. in rats w/antiserum, as it binds w/ inhibin
= INHIBIN needed w/E2 in LAP to inhit FSH
AMH - role in ovaries? (6)
-glycoprotein and 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
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 distribution in follicles (2)
IHC of adjacent section using anti-AMH staining
found higher staining (higher AMH levels) in small antral follicles compared to the big one
AMH as a regulator of normal follicle growth and development (3)
AMH has 2 windows of action on folliculogenesis:
1) Inhibits transition from primordial to primary follicles
2) 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
(over-recruitment = quicker depletion = earlier menopause)
Explain the window of opportunity (5)
Raised FSH = presents a window of opportunity
FSH threshold hypothesis:
- one follicle from the group of antra, follicles in the 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? Follicular phase gonadotrophins (3)
Image- intercycle rise in FSH
-As FSH falls, LH increases
- Dominant follicle acquires LH receptors on granulosa cells
- Other follicles do not, so they lose their stimulant = die
Which type of receptor is present in the Granulosa and Theca and what steroids are produced consequently? (4)
Granulosa:
receptors: FSHr and then LHr acquired from MF phase in dominant follicle
steroids: FSH drives oestrogen production in F phase and LH drives Progesterone in L phase
Theca cells:
receptors: LHr
steroids: LH drives Androgens and Progesterones
Integration of feedback and the menstrual cycle - graph data of Inhibin (6)
Inhibin B:
-highest in early-mid FP (ratio of activin: inhibin)
-declines in LFP (small peak at LH surge)
-zero in luteal phase.
Inhibin A:
-increases in late FP with highest levels in luteal phase (being made by CL) – contributes to inhibition of FSH in this phase
-dramatic decline in Inhibin A end of the luteal phase allows for increase in FSH
interlinked with activin (feedback)
