Menstrual Cycle II Flashcards
How does the switch to positive feedback occur? LH vs hCG (3)
1) LH surge lasts for 36-48 hours(>300pmmol threshold for 2 days)
2) triggers ovulation (timing varies from species-species)
» LH surge relatively precise predictor of timing of ovulation
3) LH is rapidly cleared from serum, in contrast to hCG (from blastocyst) which is cleared slowly & binds with great affinity to LHCGR
Where are LHr found on the follicle during follicle selection?
Theca + Granulosa cells - dominant follicle
Preovulatory Follicle changes after LH Surge and why (6)
prior:
-The eggs move into the middle- oocytes surrounded by cumulus cells (COC)
after:
-eggs move to the surface of ovary (ready for ovulation)
-loss of ovarian surface epithelium
-breakdown of underlying basal lamina, GranulosaC + ThecaC at apex (to allow rupture)
-GC basal lamina dirsrupted to allow extension of blood vessels into GC Layer + for infiltration of theca cells + leukocytes into GC compartment
-COC detaches from surrounding GC to expand
What factors are responsible for holding the oocyte in
meiotic arrest? (4)
‒ High cAMP → keep maturation promoting factor (MPF) inactive
‒ cGMP enters oocytes from cumulus cells via gap junctions to inhibit oocyte cAMP phosphodiesterase PDE3A activity (PDE3A normally degrades cAMP)
‒ H2O2/NO/calcium
‒ other cells/ ovarian environment & integrity of the follicle?
Effect of LH (7)
Within 3-12h of LH surge:
» Detachment of COC from surrounding mural GC, followed by cumulus cell expansion – formation of unique extracellular matrix between cumulus cells (aka “mucification”)
– Comprised of long chains of hyaluronan
– Visco-elastic properties of CC matrix important for successful ovulation, ovum pick up by oviducts and penetration of sperm
» ↓cGMP production and closure of gap junctions
» 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 (23 chromosomes + a bit of cytoplasm)
» Arrests again in Metaphase II
LH surge and resumption of meiosis (10)
image
pre:
-high cGMP
- high cAMP
- preventing MAF from being active
post surge:
-close channels
-decrease cGMP
-activate PD3EA
-degraded cAMP
-GC breakdown
-meosis 1 starts
-maturation process start +finish
Meiosis in the Oocyte (6)
-Early oocytes classified as immature i.e. at germinal vesicle (GV) or metaphase 1 stage
-Meiosis I is completed with half chromosomes but nearly all cytoplasm remaining in the secondary oocyte
- Remaining chromosomes move with small bag of cytoplasm to form discarded polar body (PB)
-Chromosomes of secondary oocyte immediately enter 2nd
meiotic division, form the 2nd metaphase spindle and arrest
-This arrest is maintained by cytostatic factor (protein complex)
-Egg is ovulated in this arrested state
Why is there an unequal division of cytoplasm? (women>men)
All organelles, mitochondria (maternal mitochondria) - all energy needed for the early stages of pre-implantation for embryo development will come from the mature oocyte
LH surge & Ovulation - stigma creation (5)
-LH surge induces expression of progesterone receptor (PR) in GC = luteinisation of DF cells (both granulosa and theca)
-E2 production falls and P is stim. (because granulosa and theca luteal produce p)
-Blood flow to the follicle increases & new vessels appear in avascular GC
-Prostaglandins and proteolytic enzymes (e.g. collagenase and
plasmin) increased in response to LH and progesterone to digest collagen in follicle wall
-appearance of apex or stigma on ovary wall
» 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)
Ovulation-post cascade of events (5)
Cascade of events → release of COC → Ovulation
1)Increased secretion of chemokine/cytokines from GC & TC triggers massive infiltration of leukocytes from circulation →
acute inflammatory response
2 )In humans – ovulation occurs randomly from either ovary during a given cycles, some indication more common from right ovary
(Progesterone essential for ovulation
» Progesterone inhibitor (RU486) suppress ovulation)
3)Prostaglandins-E and -F and hydroxyeicosatetraenoic acid (HETE metabolite of arachidonic acid) reach a peak level in follicular fluid just prior to ovulation
4) Prostaglandins stimulate proteolytic enzymes (proteases)
5) HETEs may stimulate angiogenesis and hyperemia (↑blood flow)
Follicle Rupture/Ovulation (2)
No increase in intra-follicular pressure
Progressive weakening of stigma region and OSE overlying follicle prior to rupture – fundamental aspect
What is involved in the rupture of the ovarian wall? (3)
1) LH stimulates secretion of Plasminogen Activator (PA)
2) Collagenase disrupts fibril network of theca & tunica albuginea & promotes digestion of basement membrane of follicle and OSE
3) TNF-alpha induces cell death, proteolysis, stigma formation and eventual follicular rupture
Ovulation pt2 (6)
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
Ciliated cells are controlled by which hormones?
Residual part of follicle collapses into space left by fluid – a clot forms and whole structure become corpus luteum
Inflammation Associated with Ovulation - effects (4)
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!
How does the ovulatory ‘wound’ heal after rupture? (3)
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 – mitogenic (oestrogen)?
-Recently identified stem cell/progenitor population that may contribute to maintenance of OSE
Signs of Ovulation - Why do you need to keep a chart of basal body temp from day 1 of LMP? (6)
A slight rise in basal body temperature, typically 0.5 to 1
degree, measured by a thermometer (temp measured everyday)
Tender breasts
Abdominal bloating
Light spotting
Changes in cervical mucus
Slight pain or ache on one side of the abdomen
Cervical Mucus Ovulation Sign-The cervical mucus or cervical fluid changes throughout MC (6)
-Immediately after menstruation, the cervical mucous is scant and viscous.
-In late follicular phase, ↑ E2 levels, the cervical mucous becomes clear, copious and elastic.
-Quantity ↑ 30 fold compared to EFP
-The stretchability/elasticity of cervical mucous evaluated between two glass slides and recorded as the spinnbarkeit
-After ovulation, ↑progesterone levels, the cervical mucous again, becomes thick, viscous and opaque and ↓ quantity produced
Ovulation Prediction (5)
mean follicular phase length was 16.9 days (95% CI: 10-30)
mean luteal phase length was 12.4 days (95% CI: 7-17)
Mean cycle length was 28 days (range: 23–35); 34% of women
believed they had a 28-day cycle, but only 15% did.
Ovulation day varies considerably for any given menstrual cycle length; thus it is not possible for calendar/app methods that use cycle-length information alone to accurately predict the day of
ovulation.
In order to identify the fertile period, it is important to track
physiological parameters such as basal body temperature and not just cycle length.
Menstrual cycle and covid (3)
images
slight increase (half a day) in period length in vacc compared to unvaccinated
went back to normal in next or next 2 cycles
menses length didn’t vary
What are you measuring when using Ovulation Prediction Kits (2)
measuring LH but some measure E3G too.
E3G is urinary metabolite of oestradiol, allowing women to
identify days of high fertility leading up to ovulation
Fertile period spans 6 days and is affected by: (3)
– Lifespan of the egg → up to 24h after ovulation
– Lifespan of sperm → median=1.5days but sperm can survive up to 5 days in the sperm supportive mucus of fertile days of cycle » sperm
survival is dependent on the type & quantity of mucus within cervix AND the quality of the sperm
What is lutein?
After ovulation, remaining granulosa enlarge, become
vacuolated in appearance, and accumulate a yellow pigment
called lutein
CL & Luteal phase (3)
-Massive angiogenesis to form new capillaries
-The luteinized granulosa cells combine with newly formed theca
-lutein cells and surrounding stroma in the ovary to become the corpus luteum (CL).
