Folliculogenesis/Menstrual Cycle Flashcards
At what stage does the oocyte arrest in the 3-5 mo fetus? What is this oocyte callled?
Prophase I (4C, 2N) Germinal vesicle
When does meiosis 1 resume?
LH surge
If egg unfertilized, in what stage does it arrest?
Metaphase II (2C, n)
Characteristics of the oocyte at ovulation?
1N/2C, secondary oocyte, first polar body extruded
What stage oocyte is capable of fertilization?
Metaphase II of meiosis II
What happens when sperm fuses with oocyte membrane?
Cortical reaction modifies ZP to block polyspermy by cortical granule release of enzymes that digest sperm receptor glycoproteins ZP2 and ZP3 so they can no longer bind sperm
What is a primordial follicle?
- Oocyte arrested in diplotene of mitotic prophase
- Surrounded by single layer of flattened pre-granulosa cells (prevent atresia)
How do TGF-beta family proteins (4) influence primordial follicles? (which ones promote development, which ones inhibit development?)
- Activins – promote primordial develop
- Inhibins – inhibit primordial develop
- AMH – inhibits primordial development
- BMPs – promote primordial development
How do neurotrophins (4) influence primordial follicles?
(NGF, BDNF, NT-3, NT-4/5) bind trk proto-oncogene family to promote development
How does FOXL-2 influence primordial follicles?
- Essential for granulosa cell differentiation
- Causes blepharophimosis/ptosis/epicanthus-inversus syndrome
- Affects eyelid and causes premature ovarian failure
How does kit-ligand influence primordial follicles?
- Expressed on GCs of growing follicles
- Mutations lead to failure of follicular growth beyond primary stage
General structure of primary oocyte
Oocyte surrounded by a cuboidal layer of granulosa cells
What are gap junctions in the primary oocyte?
Collections of intercellular membrane channels that allow adjacent cells to share small molecules (< 1 kDa). Gap junction channels are composed of connexins, a homologous family of more than 20 proteins. Located btwn granulosa cells and btwn granulosa cells and oocytes.
Name 2 of the most important connexins in primary oocyte and their location
Connexin-37 and connexin-43: form gap junctions with different permeability properties.
Connexin-37: predominant connexin in the oocyte
Connexin-43: predominates in granulosa cells
Layers of theca cells in secondary follicle
- Theca interna (closest to basal lamina)
- Theca externa (furthest from basal lamina)
Theca cells express genes for what hormone and which has the highest output?
Androgen production, androstenedione
What enzyme evidence in theca/granulosa cells supports the 2-cell, 2 gonadotropin explanation for estrogen production?
Presence of P450c17 (17alpha hydroxylase) only in theca and P450arom (aromatase) only in granulosa
Name 2 gonadotropin independent signals in primary follicle
GDF-9, BMP-15
What is GDF-9 and where is it expressed?
TGF-beta family protein – highly expressed in oocytes; lesser extent in GCs
• Signals via serine-threonine kinase receptors, produced by oocytes in primary and larger follicles but absent in primordial follicles
• Mutation in mice prevents follicle development beyond primary stage and absence of thecal markers, and eventual oocyte death
What does BMP-15 do and when does its action start?
- Promotes growth and maturation of follicles
- Starting in gonadotropin independent phase (primary follicle)
Characteristics of secondary/pre-antral follicle
Ongoing granulosa cell proliferation (2nd layer forms)
theca layer forms; vascular supply develops
Increase in oocyte size
Presence of FSH receptors (needs FSH to form antrum)
Hormone signaling to secondary/pre-antral follicle?
FSH: Required beyond two layers of granulosa cells
• FSH acts via FSH-R in adenylate cyclase system
• This induces aromatase and causes estrogenic microenvironment
• FSH and estrogen act synergistically to up-regulate FSH receptors
• The relative estrogen/androgen ratio determines the fate (grown vs. atresia) of the follicle