Menstrual Cycle I Flashcards
What is needed for correct menarche to occur?
Pulsatile release of both GnRH and gonadotrophins is key in maintaining HPG axis
Continuous release causes cessation
How is length of menstrual cycle measured?
The number of days between first day of menstrual bleeding of one cycle to onset of menses of the next cycle
What are the stages of the menstrual cycle?
- menses
- follicular phase
- ovulation
- luteal phase
What is the median duration of menstrual cycle?
Median duration of MC is 28 days with most cycles between 25=30 days
How long does menstruation last?
Menstruation lasts 3-8 days, written as 7/28 or 5-6/27-32
What is polymenorrhea?
MC < 21 days = polymenorrhea
What is oligomenorrhea?
MC>35 days=oligomenorrhea
When does the menstrual cycle become expectedly irregular
Menstrual cycle typically most irregular around extremes of reproductive life i.e menarche and menopause
Describe the levels of FSH throughout the cycle
FSH rise (MF) coinciding with antral follicle recruitment
Peaks with LH surge
Suppressed completely during luteal phase
How do LH levels change during the menstrual cycle?
LH rises with an exponential peak (LH surge), suppressed during luteal phase
Why do E2 levels rise?
E2 levels rise due to increase in antral follicle no. secreting more oestrogen
Large exponential rise due to dominant follicle selection → LH surge
Which hormone dominates the luteal phase?
Progesterone dominates luteal phase as secreted from CL.
Rise due to ovulation and demise due to lack of fertilisation
Which steroids are produced by the ovary?
Theca - androgen production
Granulosa - oestrogen production
Why do only granulosa cells produce oestrogen?
Aromatase only available in GC
What causes antral follicles to grow?
Selective FSH rise causes selection of antral follicles to grow
How does the dominant follicle survive?
Growing follicles pump out E2 (-ve) decline in FSH causes DF to survive only
How does DF survive and grow?
DF grows exponentially (MF) pumps out lots >300pmol of E2 (+ve) - LH surge
Ovulation of mature oocyte
What happens to remaining follicles (not DF)?
Remainder of oocyte converted into CL secreting P > E2 (-ve)
Describe the cyclical nature of mammals
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
Which mammals undergo menses?
Menstrual cycles occur only in humans, primates (apes and monkeys)
Named for regular appearance of menses i.e. shedding of the endometrial lining
What is meant by oestrous cycles?
The cyclic appearance of behavioural sexual activity (heat or oestrus)
No menstruation – the endometrium is reabsorbed if fertilization does not occur
Describe the feedback mechanisms of the HPO axis
-ve / +ve feedback from E2 & P
But also +ve/-ve feedback from activins and inhibins
Where is inhibin produced?
Produced by testis (Sertoli cells) and ovary (Granulosa cells)
Describe the structure of inhibin
Disulphide-linked protein dimers
Common α-subunit with different β-subunits giving two forms of Inhibin
How do inhibins affect FSH secretion?
Both forms specifically suppress FSH secretion by pituitary without affecting LH secretion
Where are activins found?
Isolated Activins from follicular fluid
What is the role of activin?
stimulate FSH secretion
What is follistatin?
Another FSH-suppressing protein from follicular fluid
How does Follistatin produce its FSH-suppressing efefcts?
Binds activin with high affinity » neutralizes FSH-stimulating ability of activin
How are inhibis and activins produced?
Biosynthesis of inhibins and activins occurs from 3 genes, makes precursor protein:
> from TGFb superfamily
- a-protein specific for inhibin
- Ba-protein can form either activin / inhibin
- Bb-protein can form either activin / inhibin
What are the different forms of inhibin?
Inhibins take 2 forms depending on β-chain composition
- Inhibin A and Inhibin B
What are the various forms of activins?
Activins take 3 forms depending on β-chain composition
Activin A (βA-homodimer), Activin B (βB-homodimer) Activin AB (βAβB-heterodimer)
Which cells secrete activin / inhibin?
Activin and inhibin released by granulosa cells
How does activin:inhibin ratio change throughout the menstrual cycle?
Ratio of Activin:Inhibin decreases as the cycle progresses
- Activins = ↑FSH in EFP
- Inhibins = ↓FSH in LFP
What other factor can affect activin activity?
Activin activity can be further regulated by how much follistatin is in the follicular fluid - can bind and reduce activity
Describe the follicle size in the late follicular phase
Late follicular phase corresponds with larger antral follicles
What is AMH?
Anti-Mullerian Hormone is a glycoprotein and member of the TGFβ superfamily
When is AMH expressed in males?
In males expressed from week 8 of development; causes regression of Müllerian ducts by a wave of apoptosis
Where is AMH secreted in the ovaries?
Expressed by ovarian granulosa cells with levels peaking in selectable follicles
(large preantral and small antral follicles) » then decreasing
AMH produced primarily in early antral follicles and then dies off as follicles grow
What are the 2 actions of AMH on folliculogenesis?
- Inhibits transition from primordial → primary follicles
2. Inhibits FSH-dependent cyclical recruitment of follicles
What is the evidence that AMH limits primordial-primary follicle transition?
Born with resting primordial follicles - slowly activate and grow
k/o AMH = follicle growth
How does AMH inhibit FSH-dependent recruitment of follicles?
Inhibits FSH-stimulated aromatase and FSH receptor expression → in normal cycle would act to prevent over-recruitment of growing follicles
Describe the process of follicular growth of preantral follicles
Preantral follicular growth occurs continuously once follicles activated
Grow slow + regulated - reach point where FSH required
↑FSH = desired size follicles continue to grow and enter next stage - smaller cohort chosen
Outline the growth of antral follicles and the DF
Antral follicles grow
Granulosa cells multiply
Activins activated to enhance stimulation + follicle growth
Follicles grow = E2 production and inhibins resulting in -ve feedback = ↓FSH
⇒ dominant follicle selected as other follicles in cohort die away due to lack of FSH
What stimulates dominant follicle selection?
Raised FSH present a “window” of opportunity
E2 levels rise reinstating negative feedback at pituitary causing FSH levels to fall prevents further follicle growth
How does the DF survive the lack of FSH?
As FSH falls, LH increases.
Dominant follicle acquires LH receptors on granulosa cells.
Other follicles do not, so they lose their stimulant and die.
Which androgens are stimulated by gonadotropins during the menstrual cycle phases?
Follicular phase
- FSH drives oestrogen production
Luteal phase
- LH drives progesterone
Which receptors are expressed by Granulosa cells?
Granulosa have FSHr
Later acquire LHr in mid-follicular phase onwards
Which receptors do theca cells express?
Theca always has LHr, never FSHr
Describe how the levels of inhibin B vary in the menstrual cycle
highest in early-mid FP
- (activin: inhibin)
Declines in LFP - small peak at LH surge
Zero in luteal phase
Outline the levels of inhibin A in the menstrual cycle
Increases in late FP
Highest levels in luteal phase (made by CL) – contributes to inhibition of FSH.
Decline in Inhibin A at end of luteal phase allows for FSH increase
What other factors provide energy for mothers during pregnancy?
Pregnancy is an energy demanding process for mother - requires input from adipose tissues, insulin etc.
How may pathophysiological processes get disrupted during pregnancy?
If the mother becomes:
- Anorexic: exercise induced /eating disorders
- Overweight: insulin resistance
Why do changes occur in the reproductive tract during menstrual cycle?
Characteristic changes occur in reproductive tract tissues due to varying concentrations of E2 & P in different parts of MC
Which areas of the reproductive tract are affected by menstrual cycle hormonal changes?
Endometrium
Oviduct/Fallopian tubes
Cervix
Vagina: changes in vaginal epithelial cells
