Prenatal follicugenisis Flashcards
Why would animal models not always be accurate for humans?
many animals are poly-ovulatory so may not be accurate for humans
How may folliculogenesis be studied?
- Animal models
- Genotype/phenotype associations in naturally occurring mutations or from knock-out mice
- Culture of whole ovaries/slices/biopsies/follicles/cells
Why are ovary cultures hard to create?
o Very difficult in human because of limited supply of tissue
o Primary cells difficult to obtain, granulosa cell line but no suitable theca cell line
Where are the eggs in a 3/4 week human embryo?
Epiblast cell in yolk sac at base of allantois differentiate into PGC (primordial germ cells)
Where are the eggs in a 5/6 week human embryo?
Mitotically dividing PGCs migrate along dorsal mesentery of hind gut to colonise genital ridge → chemotactic substance secreted by ridge to attract PGCs. It maybe Kit ligand (KL) as the receptor cKit is present on surface of PGCs
What are “nests”?
cytoplasmic bridges between mitotically dividing oocytes form syncitia/nests
What is the role of nests?
- To exchange organelles
- Not sure
Why is retinoic acid important?
It’s a key extrinsic regulator of germ cell entry into meiosis
What gene’s expression increases before meiosis?
- DAZL expression increases before meiosis at 9-14 weeks gestation.
- DAZL mutations in humans are associated with sub-fertility
Name the steps before [primordial follicle formation
- Germ cell cyst formation
- Meiotic onset
- Cyst breakdown/primordial follicle formation
What happens during the cyst breakdown?
the nests breakdown and surrounding cells will infiltrate around the oogonia to form the primordial follicles – this happens before birth in humans
How do primordial follicles form?
Syncytia breakdown & somatic cells invade to surround oogonia to form primordial follicle (PF) – this all happens on the genital ridge
What regulates PF formation?
o FIGLA k/o female mice sterile with no PF
o Activin βA expression ↓ just before nest breakdown. Downstream of Activin βA is TRKβ receptor, which if k/o → loss of oocytes → “streak” ovaries, contrast with male as can have testes with no sperm
o Co-ordination of signalling pathways: KIT, Notch and TGFβ
o Hormones – FSH promotes formation of primordial follicles and E2 and P oppose
Summarise formation of follicles?
Germ cell migration»_space; colonisation of ovaries»_space; formation of the follicles
What happens to oocytes and follicles right before birth?
Massive loss/apoptosis of oocytes and follicles right before birth
Why does that massive loss/apoptosis of oocytes and follicles happen right before birth?
- Failure of mitosis/meiosis involving defective chromosome spindle function
- Unrepaired DNA damage during egg/follicle formation
- Insufficient pre-granulosa cells resulting in naked oocytes which degenerate
- Degeneration of oocytes during nest breakdown and follicle formation.
What is the ovarian reserve?
Once formed primordial follicles represent the entire pool of germ cells available during reproductive life of the female - this is the ovarian reserve
What are the different stages of follicle growth?
- Resting
- Preantral
- Antral
- Ovulatory
What is germ cell selection?
to select oocytes of the highest quality for the ovarian reserve
Describe what happens as the primordial follicles grow
- All the resting primordial follicles are in the avascular ovarian cortex
- blood vessels are only on the hilum of the ovary
as follicles grow they move in towards the blood supply - after dominant follicle selection and it’s ready to ovulate it moves out towards the periphery and outer cortex
What happens in the resting stage?
Resting follicles are in meiotic arrest
What happens in the preantral stage
Resting follciles grow slowly to become preantral follicles - no gonadotrophins needed
What happens in antral stage?
At early antral stage gonadotrophins are needed – cohorts of follicles are recruited in the menstrual cycle, grow and a dominant follicle is selected