5. Ovarian follicle development

Question 1

Define what is PGC?

Answer 1

Primordial germ cell (PGC) - sex undetermined germ cell - bipotential

Question 2

Define what are oogonia?

Answer 2

Oogonia - mitotic PGCs that have already went into a developing ovary

Question 3

Define what is an oocyte

Answer 3

Oocyte - oogonia which have stopped mitotic divisions and started meiosis

Question 4

Define what is an egg

Answer 4

Egg - an ovulated oocyte

Question 5

How are oogonia nests / cysts formed?

Answer 5

Mitotic oogonia become surrounded by somatic cells - stroma penetrates into the developing ovary and spreads laterally below the surface

Question 6

How is cytoplasmic movement possible in oogonia nests / cysts?

Answer 6

In germ cell (oogonia) nests / cysts oogonia have cytoplasmic connections to each other - because of incomplete cytokinesis

Question 7

What signal induces oogonia to stop mitosis and enter meiosis?

Answer 7

In sex determination - fetal kidney - mesonephros - secretes retinoic acid (RA) into neighbouring developing ovaries - signals for oogonia to stop mitosis and induce meiosis

Oogonia -> oocytes when RA signaled

Question 8

How does retinoic acid define the finite pool of oocytes?

Answer 8

Retinoic acid (RA) stops mitosis and induces meiosis - end of mitosis defines finite pool of oocytes

Question 9

Compare male vs female meiosis

Answer 9

Question 10

How do oocytes become enclosed in follicles?

Answer 10

Oocytes become enclosed in follicles during germ cell nest breakdown

Question 11

How is the majority of oocytes lost and why?

Answer 11

In germ cell breakdown somatic cells invade nests / cysts and surround oocytes - but majority of oocytes die and don’t form follicles - could be because not enough somatic cells to form a follicle for each oocyte

Question 12

When are follicles formed in humans vs other species?

Answer 12

In humans: follicles formed around mid-pregnancy
In mice: at the time of birth

Question 13

What is the resting state of primordial follicles?

Answer 13

Primordial follicles enter resting state - meiotic arrest - can stay in resting state indefinitely - resting pool of follicles - until are activated in the ovary -> matured -> ovulated ——> eventually pool used up

Question 14

How does growth initiation (activation) begin in primordial follicles?

Answer 14

Gradual movement out of resting state - oocyte grows + granulosa cells round up and undergo mitosis

Strongest regulation from PTEN signalling pathway - keeps primordial in resting - when interfered -> growth initiation (activation)

Question 15

What is the change of a pre-antral to antral follicles?

Answer 15

Follicle increases in size, granulosa cells morph form flat into round, granulosa cells multiply

Question 16

What makes a follicle antral?

Answer 16

Pre-antral follicle becomes antral when it forms antral cavity - fluid filled

Question 17

What is the antral cavity needed for?

Answer 17

Follicles are avascular - replaces blood function - excretion / nutrition

Question 18

What is the structure of an antral follicle?

Answer 18

oocyte
antral cavity
granulosa cells (cumulus + mural)
basement membrane
zona pelucida
theca

Question 19

What are the two types of granulosa cells?

Answer 19

• cumulus granulosa cells - around oocyte
• mural granulosa cells - steroidogenically active

Question 20

What is the full cycle of follicle maturation up until ovulation?

Answer 20

Question 21

When does meiosis resume in oocytes?

Answer 21

Meiosis resumes when oocyte is ready to ovulate - meiosis II complete after fertilisation

Question 22

Does RA from mesonephros affect testicular development?

Answer 22

Mesonephros secretes RA but testes not affected because RA degraded

Question 23

What contributes to primordial follicle activation?

Answer 23

Granulosa cells of growing follicles secrete AMH - inhibit other follicle recruitment for development and ovulation
—> few growing follicles - few AMH - follicles less-inhibited - self-regulating system

PTEN inhibition (activation) <-> AMH (inhibition) balance

Question 24

What are the main hormones regulating follicle development

Answer 24

Hormonal control - follicle stimulating hormone (FSH) and luteinising hormone (LH)

Question 25

What are the main functions of FSH and LH in follicle development?

Answer 25

**FSH** - required for **antral follicle growth** **LH** - stimulates **final stage follicle development** + **ovulation** but FSH and LH **not needed for early follicle growth** - gradual decline of primordial follicle pool is not affected by endocrine system - **regulates antral follicles** - the **pill interferes with later follicle stages** not primordial follicle loss

Question 26

How does the system regulate how many oocyte ovulate?

Answer 26

**Litter size regulated** by **competition between follicles** - **follicle dominance** - group of follicles in mid-antral stage - **some more ahead** in development: - **more blood vessels** to their **thecal** layer - get **more FSH** - **more FSHRs** -> follicle **starts secreting oestrogen** —> **FSH falls** - other - **subordinate** - **follicles not supported**

Question 27

How do dominant follicles inhibit subordinate follicle development?

Answer 27

**Dominant** follicle **secretes oestrogen** - **inhibits FSH** production (little decrease in the graph) - other **subordinate follicle growth not supported** - undergo **atresia** - atritic follicles

Question 28

What is the main signal for ovulation?

Answer 28

Increase in LH + FSH

Question 29

Explain how sex specific genomic imprinting occurs

Answer 29

1. Supression/activation **erasure in primordial germ cells** 2. **Imprint establishment** depending on embryo sex (birth-> puberty) 3. In reproduction both **gametes** with different imprints **form zygote** -> **blastocyst** 4. **Monoallelic expression** but **genetic imprinting compatibility** between males and females - expression of needed genes ensures **normal development**