Menstrual cycle 2 Flashcards
Discuss the switch of E2 to positive feedback and the LH surge
At the end of the follicular phase E2 feedback becomes positive causing exponential rise in LH which need to exceed a threshold (required for ovulation)
LH surge will last for 36-48 hours. This will trigger ovulation.
The LH surge is a precise predictor of ovulation
LH is cleared from serum in contrast to hCG which is cleared slowly and binds with great affinity to LHCGR
(Luteinizing hormone/choriogonadotropin receptor)
What releases hCG?
The growing placenta -the embryo
The hCG will maintain the corpus luteum
Where are LHr found on the follicle?
They are found on both theca and granulosa cells
How does the structure of a preovulatory follicle differ following LH stimulation prior to ovulation?
There is a loss of OSE (Ovarian surface epithelium).There is also a breakdown of underlying basal lamina and GC and TC at apex to allow for rupture.
This will allow the invasion of blood vessels into the follicle.
Granulosa cells do not have vasculature but theca cells do.
GC (granulosa cells)basal lamina is disrupted allowing extension of blood vessels into GC layer and for infiltration of theca cells and leukocytes into GC compartement.
COC detached from surrounding GC to expand.
At what point will the oocyte come out of meiotic arrest and undergo meiosis 1 ?
This will occour during the LH surge
What factors regulate the meiotic arrest of follicles?
1.High cAMP-This keeps the maturation promoting factor (MPF) inactive
What keeps cAMP high is :
2.cGMP enters oocytes from cumulus cells via gap junctions to inhibit oocyte cAMP phosphodiesterase PDE3A activity(PDE4A normally will degrade cAMP)
- H202/No/Calcium
- Other cells /ovarian environment
What are the effects of the LH surge ?
Within 3-12 hours of the LH surge:
1.There is a detachment of the COC from surrounding mural granulosa cells, followed by cumulus cell expansion=the formation of the unique extracellular matric between cumulus cells (mucification) -this makes the complex sticky
- This is comprised of long chains of hyalyuronan
- Visco-elastic properties of CC matrix improtant for successful ovulation,ovum pick up by oviducts and penetration of sperm
How does Lh surge lead to the ceasation of meiotic arrest?
There will be an activation of PDE3A which causes a reduction of cAMP.This leads to activation of pathways leading to the breakdown of nuclear membrane in primary oocyte (germinal vesicle breakdown)
This will cause the resumption of meiosis in the oocyte -com0pleted meiosis and the release of the first polar body
Arrests again in Metaphase 2
Outline the uneven division during meiosis of an oocyte
The early oocytes are classified as immature at germinal vesicle or metaphase 1 stage
Meiosis 1 is completed with half chromosomes but nearly all cytoplasm will remain in the secondary oocyte
The remaining chromosomes will move with small bag of cytoplasm to form discarded polar body
Why do we have an unequal division of cytoplasm ?
There is unbalanced division to form polar bodies so that the egg will contain enough nutrients for early embryonic development. This includes mitochondria which is why we get all our mitochondrial DNA from our mother.
Polar bodies can be tested for chromosomal abnormalities during IVF. However, these will only detect if errors of meiosis 1.
What will happen following resumption of Meiosis during LH surge ?
Chromosomes of the secondary oocyte immediately enter 2nd meiotic divison and will form the 2nd metaphase spindle then arrest.
This arrest is maintained by cytostatic factor(protein complex)
Egg is ovulated in this arrested state
What will happen following resumption of Meiosis during LH surge ?
Chromosomes of the secondary oocyte immediately enter 2nd meiotic divison and will form the 2nd metaphase spindle then arrest.
This arrest is maintained by cytostatic factor(protein complex)
Egg is ovulated in this arrested state
What are some of the main effects of the LH surge during ovulation?
The LH surge will induce expression of progesterone receptor (PR) in the granulosa cell in all species and result in luteinisation of DF (dominant follicle) cells (both granulosa and theca)
The Oestrogen production will fall and progetseron is stimulated
Blood will flow to the follicle and this increases and new vessels appear in avascular granulosa cells
Prostaglandins and proteolytic enzymes e.g collagenase and plasmins are increased in response to LH and progesterone
What are the roles of collagenase and plasmin
Digest the collagen in follicle wall
This causes the appearance of the stigma /apex which is the point of the fominant follicle which is closest to the ovarian surface where digestion occours
Outline how ovulation is an inflammatory process
There is a cascade of events which leads to the release of the COC -this leads to ovulation
Increased secretion of chemokine/cytokines from granulosa cell and theca cell triggers massive infiltration of leukocytes from circulation
(Acute inflammatory response)
In humans -oculation occours randomly from either ovary during a given cycle some indication more common from right ovary
Progesterone is essential for ovulation
(progesterone inhibitor (RU486) will suppress ovulation.
Prostaglandins-0E and F and hydroxyeicosatetraenoic acid