L6: Ovary 1: Ovarian Follicle Development Flashcards
What are primordial germ cells?
Germ cells in mammals that have not gone down sex differentiation
What is oogonia?
When PGCs get to gonad which is within female, they are then called oogonia. They are still undergoing mitosis.
What is oocyte?
When mitotic division stop and meiosis starts is then called oocyte
What is an egg?
When ovulated, unless or until fertilised, called egg
What type of germ cells are found in the developing, fetal ovary?
Initially, oogonia, still undergoing mitosos, become surround by somatic cells, forming nests.
Within these nests, there are ‘cysts’ of germ cells that have cytoplasmic connections to each other, due to incomplete cytokinesis.
What is mesonephros?
fetal kidney, cells coming to gonads from mesonephros
What does mesonephros produce?
retinoic acid
Does retinoic acid have any effect in males?
No effect on prespermatogonia, but degraded by Sertoli cells
What does retinoic acid do in females?
Induces oogonia to stop undergoing mitosis and start meiosis, germ cells are now called oocytes
How does meiosis between males and females differ? Explain meiosis
In males as normal meiosis, in females different. First stage is the same oogonium duplicates its genome (meiotic arrest). Then there’s first and second meiotic divisions. At first meiotic division there is 1st polar body (all that it has is excess chromosomes). During second division, 2nd polar body produced. End result in females is 1 haploid cell and 2 polar bodies. In males you get 4 haploid cells.
Meiosis in female germ cells results in production of only one mature germ cell, and only completes that process around the time of fertilization.
When does development of germ cells till oocytes take place?
Fetal ovary stage
Why does ovary have a finite pool of oocytes?
Because female germ cells have stopped mitosis in fetal ovary stage.
End of mitosis underlies major difference between females and males re-strategy for producing germ cells.
What’s the difference between meiosis of male and female germ cells?
meiosis in female germ cells results in production of only ONE mature germ cell, and only completes that process around the time of fertilisation
When does meiotic arrest take place?
Before first meiotic division. Within follicle, chromosomes have replicated, but oocyte entered and maintained in meiotic arrest while enclosed within follicle.
Any one oocyte will remain in meiotic arrest for the entire time from when it first became enclosed in a follicle - before birth in most species all the way through to when it is ovulated - which for some oocytes will not be until the very end of the female’s reproductive lifespan.
What happens during follicle formation?
Somatic cells now invade cysts, and surround individual oocytes. Most oogonia do not make it to follicles, so it is accompanied by massive wave germ cell death (lost vast majority)
Why is there a massive wave of germ cell death during follicle formation?
Not sure why there is a massive death, one theory is that there are not enough somatic cells to cover each oocyte.
What is a primordial follicle?
Oocyte surround by single layer granulosa cells
When do primordial follicles form?
- In some species, e.g. humans – follicles are formed around mid-pregnancy
- In other species, e.g. mice – follicles are formed around the time of birth
- But whenever birth occurs, once follicle formation is completed, the ovary has a finite pool of follicles that cannot be replenished
When does zona pellucida form?
As primordial follicle forms, between oocyte and granulosa cells
What is the resting state of primordial follicles?
Primordial follicles are able to stay in the state from birth in meiotic arrest pretty well indefinitely
What happens during initiation of follicle growth?
Gradual movement of primordial follicles out of resting pool, to start to grow and develop.
As follicle starts to grow, oocyte grows, granulosa cells round up and undergo mitosis
What keeps primordial follicles at their resting state?
PTEN signalling pathway, it keeps primordial follicles at that stage - interfere with pathway, all primordials undergo growth initiation: within a very short time, none left
How are follicles called at early stages of development and why?
Pre-antral follicles, because they don’t have antral cavity yet.
What structures do pre-antral follicles have and what happens to them?
- granulosa cells - continue to divide
- oocyte continues to grow (but remains in meiotic arrest throughout
- Basement membrane round follicle (barrier to blood vessels, and to large molecules, but small molecules can pass through
- thecal cells outside basement membrane, come from interstitial tissue
The structure is as follows:
- oocyte
- granulosa cells
- basement membrane
- thecal cells
How are mature and ready to ovulate follicles called?
Antral follicles
What’s the structure of antral follicle?
- antral cavity - fluid-filled
- granulosa cells - continue to undergo mitosis, increasing in number
- large oocyte usually fully grown by now. Still with double set of chromosomes producing lots of mRNAs, proteins which will later to help support early embryonic development
- basement membrane
- theca cells
Why do antral follicles need antral cavities?
Fluid is almost certainly substituting for blood supply since everything inside basement membrane is avascular. Antrum starts of with small patches which then coalesce together, ending up with horse-shoe shaped when follicle is fully grown
What are the two types of granulosa cells? Where are they located in antral follicles?
Granulosa cells differentiate further into two different kinds:
- cumulus granulosa cells - interact with oocyte
- mural granulosa cells - very steroidogenically active, interact with rest of ovary
What is atresia?
Follicles / cell death
How are follicles ready to ovulate called?
When antral follicle is fully grown, ready to ovulate it is called pre-ovulatory or Graafian follicle
What is the other factor (other than PTEN signalling) that makes most primordial follicles stay at that resting stage most of the time?
Signalling from growing follicles:
AMH (anti Mullerian Hormone). Granulosa cells of growing follicles secrete AMH, particularly at the pre-antral follicle stages, and AMH can also inhibit the growth initiation of primordial follicles.
Therefore, if there are very few growing follicles, there will be little AMH secreted.
And if there are only low levels of AMH, then growth initiation of the primordial pool will be less inhibited, leading to more follicles growing, building numbers of growing follicles back up
How is FSH important in follicle growth?
FSH REQUIRED for antral follicle growth, it is not necessary for pre-antral stages
How is LH important in follicle growth?
LH can stimulate final stage follicle development (don’t necessarily need) and REQUIRED for ovulation.
What is follicle dominance?
This is the system regulating litter size in mammals. It is due to competition between follicles, only some follicles selected for continued development - the dominant follicles
How are the follicles that lose dominance called?
Subordinate follicles
How does follicle dominance happen?
Within a group of growing follicles at the mid-antral stage, some are more ahead developmentally, with:
- more blood vessels to their thecal layer (and therefore more FSH etc available to cross basement membrane into follicle)
- more FSH receptors
- mural granulosa cells that have started to express LH receptors
these follicles become dominant. They do so just as circulating levels of FSH are falling (take up all FSH, when falls they die)
How do dominant follicles bring about the fall in FSH, through an endocrine loop?
As dominant follicle gets bigger, produces more oestrogen. Oestrogen causes negative feedback on hypothalamus-pituitary, thus FSH falls.
