5. Ovarian follicle development Flashcards
Define what is PGC?
Primordial germ cell (PGC) - sex undetermined germ cell - bipotential
Define what are oogonia?
Oogonia - mitotic PGCs that have already went into a developing ovary
Define what is an oocyte
Oocyte - oogonia which have stopped mitotic divisions and started meiosis
Define what is an egg
Egg - an ovulated oocyte
How are oogonia nests / cysts formed?
Mitotic oogonia become surrounded by somatic cells - stroma penetrates into the developing ovary and spreads laterally below the surface
How is cytoplasmic movement possible in oogonia nests / cysts?
In germ cell (oogonia) nests / cysts oogonia have cytoplasmic connections to each other - because of incomplete cytokinesis
What signal induces oogonia to stop mitosis and enter meiosis?
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
How does retinoic acid define the finite pool of oocytes?
Retinoic acid (RA) stops mitosis and induces meiosis - end of mitosis defines finite pool of oocytes
Compare male vs female meiosis
How do oocytes become enclosed in follicles?
Oocytes become enclosed in follicles during germ cell nest breakdown
How is the majority of oocytes lost and why?
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
When are follicles formed in humans vs other species?
In humans: follicles formed around mid-pregnancy
In mice: at the time of birth
What is the resting state of primordial follicles?
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
How does growth initiation (activation) begin in primordial follicles?
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)
What is the change of a pre-antral to antral follicles?
Follicle increases in size, granulosa cells morph form flat into round, granulosa cells multiply
What makes a follicle antral?
Pre-antral follicle becomes antral when it forms antral cavity - fluid filled
What is the antral cavity needed for?
Follicles are avascular - replaces blood function - excretion / nutrition
What is the structure of an antral follicle?
oocyte
antral cavity
granulosa cells (cumulus + mural)
basement membrane
zona pelucida
theca
What are the two types of granulosa cells?
- cumulus granulosa cells - around oocyte
- mural granulosa cells - steroidogenically active
What is the full cycle of follicle maturation up until ovulation?
When does meiosis resume in oocytes?
Meiosis resumes when oocyte is ready to ovulate - meiosis II complete after fertilisation
Does RA from mesonephros affect testicular development?
Mesonephros secretes RA but testes not affected because RA degraded
What contributes to primordial follicle activation?
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
What are the main hormones regulating follicle development
Hormonal control - follicle stimulating hormone (FSH) and luteinising hormone (LH)
What are the main functions of FSH and LH in follicle development?
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
How does the system regulate how many oocyte ovulate?
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
How do dominant follicles inhibit subordinate follicle development?
Dominant follicle secretes oestrogen - inhibits FSH production (little decrease in the graph) - other subordinate follicle growth not supported - undergo atresia - atritic follicles
What is the main signal for ovulation?
Increase in LH + FSH
Explain how sex specific genomic imprinting occurs
- Supression/activation erasure in primordial germ cells
- Imprint establishment depending on embryo sex (birth-> puberty)
- In reproduction both gametes with different imprints form zygote -> blastocyst
- Monoallelic expression but genetic imprinting compatibility between males and females - expression of needed genes ensures normal development
