L6: Ovary 1: Ovarian Follicle Development

Question 1

What are primordial germ cells?

Answer 1

Germ cells in mammals that have not gone down sex differentiation

Question 2

What is oogonia?

Answer 2

When PGCs get to gonad which is within female, they are then called oogonia. They are still undergoing mitosis.

Question 3

What is oocyte?

Answer 3

When mitotic division stop and meiosis starts is then called oocyte

Question 4

What is an egg?

Answer 4

When ovulated, unless or until fertilised, called egg

Question 5

What type of germ cells are found in the developing, fetal ovary?

Answer 5

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.

Question 6

What is mesonephros?

Answer 6

fetal kidney, cells coming to gonads from mesonephros

Question 7

What does mesonephros produce?

Answer 7

retinoic acid

Question 8

Does retinoic acid have any effect in males?

Answer 8

No effect on prespermatogonia, but degraded by Sertoli cells

Question 9

What does retinoic acid do in females?

Answer 9

Induces oogonia to stop undergoing mitosis and start meiosis, germ cells are now called oocytes

Question 10

How does meiosis between males and females differ? Explain meiosis

Answer 10

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.

Question 11

When does development of germ cells till oocytes take place?

Answer 11

Fetal ovary stage

Question 12

Why does ovary have a finite pool of oocytes?

Answer 12

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.

Question 13

What’s the difference between meiosis of male and female germ cells?

Answer 13

meiosis in female germ cells results in production of only ONE mature germ cell, and only completes that process around the time of fertilisation

Question 14

When does meiotic arrest take place?

Answer 14

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.

Question 15

What happens during follicle formation?

Answer 15

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)

Question 16

Why is there a massive wave of germ cell death during follicle formation?

Answer 16

Not sure why there is a massive death, one theory is that there are not enough somatic cells to cover each oocyte.

Question 17

What is a primordial follicle?

Answer 17

Oocyte surround by single layer granulosa cells

Question 18

When do primordial follicles form?

Answer 18

• 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

Question 19

When does zona pellucida form?

Answer 19

As primordial follicle forms, between oocyte and granulosa cells

Question 20

What is the resting state of primordial follicles?

Answer 20

Primordial follicles are able to stay in the state from birth in meiotic arrest pretty well indefinitely

Question 21

What happens during initiation of follicle growth?

Answer 21

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

Question 22

What keeps primordial follicles at their resting state?

Answer 22

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

Question 23

How are follicles called at early stages of development and why?

Answer 23

Pre-antral follicles, because they don’t have antral cavity yet.

Question 24

What structures do pre-antral follicles have and what happens to them?

Answer 24

• 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

Question 25

How are mature and ready to ovulate follicles called?

Answer 25

Antral follicles

Question 26

What’s the structure of antral follicle?

Answer 26

• 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

Question 27

Why do antral follicles need antral cavities?

Answer 27

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

Question 28

What are the two types of granulosa cells? Where are they located in antral follicles?

Answer 28

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

Question 29

What is atresia?

Answer 29

Follicles / cell death

Question 30

How are follicles ready to ovulate called?

Answer 30

When antral follicle is fully grown, ready to ovulate it is called pre-ovulatory or Graafian follicle

Question 31

What is the other factor (other than PTEN signalling) that makes most primordial follicles stay at that resting stage most of the time?

Answer 31

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

Question 32

How is FSH important in follicle growth?

Answer 32

FSH REQUIRED for antral follicle growth, it is not necessary for pre-antral stages

Question 33

How is LH important in follicle growth?

Answer 33

LH can stimulate final stage follicle development (don’t necessarily need) and REQUIRED for ovulation.

Question 34

What is follicle dominance?

Answer 34

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

Question 35

How are the follicles that lose dominance called?

Answer 35

Subordinate follicles

Question 36

How does follicle dominance happen?

Answer 36

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)

Question 37

How do dominant follicles bring about the fall in FSH, through an endocrine loop?

Answer 37

As dominant follicle gets bigger, produces more oestrogen. Oestrogen causes negative feedback on hypothalamus-pituitary, thus FSH falls.