Menstrual Cycle II Flashcards
(44 cards)
What do high sustained levels of oestrogen do?
Switch feedback from negative to positive
How long does the LH surge last?
36-48 hours
What does the LH surge do?
Triggers ovulation - the surge must exceed a threshold for ovulation
leads to breakdown of surface epithelium of the basement membrane and digestion of theca and granulosa cells - allows invasion of blood vessels into the follicle because granulosa cells don’t have any vasculature.
LH surge allows the follicle to rupture and release the egg
LH surge induces expression of progesterone receptor (PR) in GC in all species and results in luteinisation of DF cells (both granulosa and theca) – they become luteal cells
How is LH cleared from the serum?
Rapidly compared to hCG which is cleared slowly because it has a greater affinity to LHr
What can the LH surge be used for?
To predict ovulation
Where are the primordial follicles usually found?
In the outer cortex
What happens as the primordial follicles grow?
They will move into the ovary - near the rich blood supply
Where does the DF follicle move?
It will move back up to the surface of the ovary for ovulation
DF is under the ovarian surface epithelium, resting on the basement membrane
What factors are responsible for holding the oocyte in meiotic arrest?
o High cAMP within follicle → keeps maturation promoting factor (MPF) inactive
o cGMP enters oocytes from cumulus cells via gap junctions to inhibit oocyte cAMP phosphodiesterase PDE3A activity (PDE3A normally degrades cAMP) – keeps cAMP high
o H2O2/NO/calcium
o other cells/ ovarian environment & integrity of the follicle?
What are the effects of LH within the 3-12 hours of the LH surge?
- Detachment of COC (cumulus oocytes complex) from surrounding mural GC, followed by cumulus cell expansion – formation of unique extracellular matrix between cumulus cells (aka “mucification”)
- ↓cGMP production and closure of gap junctions – LH binds to its receptors and triggers a pathway that degrades cGMP/not favour cGMP production
- Activation of PDE3A → ↓cAMP → activation of pathways leading to breakdown of nuclear membrane in primary oocyte aka germinal vesicle breakdown (GVBD)
- Resumption of meiosis in oocyte → completion of Meiosis I & release of 1st polar body
- Arrests again in Metaphase II
What is produced at the end of meiosis I?
- Both oocytes will have half the chromosomes but one oocyte will have almost all of the cytoplasm - there’s unequal division
- The oocyte will no cytoplasm is called a polar body
- one oocyte has all the cytoplasm because it has double the organelles because the sperm only brings chromosomes
- Chromosomes of secondary oocyte immediately enter 2nd meiotic division, form the 2nd metaphase spindle and arrest
What maintains the secondary oocyte arrest?
cytostatic factor (protein complex)
What happens right before ovulation?
- LH surge induces expression of progesterone receptor (PR) in GC in all species and results in luteinisation of DF cells (both granulosa and theca) – they become luteal cells
- E2 production falls and progesterone is stimulated (both P & 17α-OHP)
- Blood flow to the follicle increases & new vessels appear in avascular GC
- Prostaglandins and proteolytic enzymes eg collagenase and plasmin, are increased in response to LH and progesterone - Digest collagen in follicle wall
- appearance of apex or stigma on ovary wall
o Stigma= point of the dominant follicle closest to the ovarian surface where digestion occurs
When does ovulation occur?
12-18 hours after the peak of LH surge
How does the follicle rupture/ovulation occur?
• No increase in intra-follicular pressure. Progressive weakening of stigma region and OSE overlying follicle prior to rupture – fundamental aspect
- LH stimulates secretion of Plasminogen Activator (PA) by binding to its receptors
- PA converts plasminogen into plasmin – plasmin activates collagenase
- Collagenase disrupts fibril network of theca & tunica albuginea & promotes digestion of basement membrane of follicle and OSE
- TNFa induces cell death, proteolysis, stigma formation and eventual follicular rupture – reinforces this pathway
What is the structure of the ovarian wall where the DF rests?
OSE=simple layer of epithelial cells, which is supported by a basement membrane that lies over the TA (held together by desmosomes and gap/tight junctions). Preferential growth of the DF brings it in close apposition with the OSE.
What happens during ovulation?
- Secondary oocyte (arrested in metaphase II) with cumulus cells is extruded from the ovary
- follicular fluid may pour into Pouch of Douglas
- egg ‘collected’ by fimbria of uterine tube
- egg progresses down tube by peristalsis and action of cilia
- Residual part of follicle collapses into space left by fluid – a clot forms and whole structure become corpus luteum (CL has luteinised granulosa and theca cells)
What is associated with ovulation?
Inflammation:
• The follicular fluid is “inflammatory”
• Inflammation definitely present, but too much is detrimental
• Higher “inflammation markers” in FF associated with decreased pregnancy rate (specifically C Reactive Protein, CRP)
• Gingivitis associated with poorer IVF outcomes (study found out)
How does the ovulatory wound heal?
- Ovary faces monumental task of repairing damage caused by follicle rupture after each ovulation
- Basic steps are known but the underlying mechanisms are still unknown
- Interestingly the ovulation wounds scar, but not for long – quick resolution
- Maybe steroidogenic environment helps – oestrogen is a mitogen
- Recently identified stem cell/progenitor population that may contribute to maintenance of OSE
What are the signs of ovulation?
- A slight rise in basal body temperature, typically 0.5 to 1 degree, measured by a thermometer
- Tender breasts
- Abdominal bloating
- Light spotting
- Changes in cervical mucus
- Slight pain or ache on one side of the abdomen
Why does the cervical mucus change throughout the MC?
it responds to oestrogen and progesterone
What is the cervical mucus like after menstruation?
scant and viscous
What is the cervical mucus like during the late follicular phase?
- because of high estradiol (E2) levels, the cervical mucous becomes clear, copious and elastic.
- Quantity increases 30 fold compared to early follicular phase
What is the cervical mucus like after ovulation?
because of ↑progesterone levels from the CL, the cervical mucous again becomes thick, viscous and opaque and ↓ quantity produced
