Lecture 12: Prenatal Folliculogenesis

Question 1

How and when are primordial germ cells formed?

Answer 1

• 3-4 weeks, PGC are seen in human embryo
• Epiblast cell in yolk sac at base of allantois differentiate into PGC

Question 2

What is seen 5-6 weeks in human embryo?

Answer 2

• Mitotically dividing PGCs migrate along dorsal mesentery of hind gut to colonise genital ridge

Question 3

What may be the cause of PGC migration?

Answer 3

→ chemotactic substance secreted by ridge to attract PGCs.
- May be Kit ligand (KL) as receptor cKit is present on surface of PGCs

Question 4

What do PGCs differentiate into?

Answer 4

• Gonad becomes testes -> PGC becomes Spermatogonia
• Gonad becomes ovary -> PGC become oogonia

Question 5

Compare the timeline of formation of oocytes & follicles in mice & humans

Answer 5

• Humans: Primordial follicle formation prenatally
• Mice: Primordial follicle formation post-natally

Question 6

What occurs during formation of oocytes & follicles?

Answer 6

• During migration PGC undergo epigenetic re-progamming (genome-wide DNA de-methylation & erasure of genomic imprinting)
• Cytoplasmic bridges between mitotically-dividing oocytes to form syncytia or “nests” -> Role? exchange of organelles eg. ER & mitochondria
• Retinoic Acid (biologically active variant of Vit A) derived from somatic cells drives germ cell entry into meiosis → induces Stra8 gene expression in oogonia

Question 7

In detail, how are primordial follicles formed?

Answer 7

• Syncytia breakdown & somatic cells (from surrounding) invade to surround oogonia to form primordial follicle (PF)
• PF formation regulated through complex network of molecular signals between oocytes and somatic cells.
• Numerous transcription factors identified in mice & human eg FIGLA, Nobox & Activin βA
• Co-ordination of signalling pathways i.e. KIT, Notch and TGFβ

Question 8

Examples of signals used during primordial formation

Answer 8

• Transcription factors: FIGLA, Nobox & Activin βA
• Downstream signalling pathways i.e. KIT, Notch and TGFβ

Question 9

How do we know that certain signals are involved in certain processes?

Answer 9

• Knock out mice -> k/o gene = look at genotype & phenotype vs normal mice
• Naturally mutated mice

Question 10

What is seen just before nest breakdown?

Answer 10

• Activin βA expression ↓
• 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

Question 11

What is seen in FIGLA k/o female mice?

Answer 11

• sterile with no PF

Question 12

What is the ovarian reserve?

Answer 12

• Primordial follicles represent the entire pool of germ cells available during reproductive life of the female

Question 13

What is the ovarian reserve range and how do we get this value?

Answer 13

• Predicted range: 35,000-2,500,000 primordial follicles - - mathematical modelling & histological counting (slicing of miscarried foetus)

Question 14

Describe oocyte reserve from embryo to menopause

Answer 14

Question 15

Why does the oocyte receive deplete just before birth?

Answer 15

To eliminate ‘bad’ oocytes/follicles:
- faults /mutations
- follicle not formed correctly i.e. naked oocyte (not surrounded by GC or nests not broken etc.