antral folliculogenesis Flashcards
Preantral to Antral Follicle Transition – Formation of Theca is crucial
- Theca of follicle is envelope of connective tissue → differentiates into theca interna & externa containing vascular tissue, immune cells and matrix factors
- Theca is critical for maintaining structural integrity of follicle and delivering nutrient to avascular GC layer
Formation and differentiation of theca extremely important for preantral to antral progression. Why?
- GDF9 k/o mice (& GDF9 mutations in human & sheep) fail to develop theca layer and follicles arrest → oocyte-derived GDF9 regulating formation of theca cell layer.
- Neo-angiogenesis, hence follicle interaction with systemic endocrine factors
- Acquisition of steroidogenic function
Theca cells derived from 2 different sources in the embryonic gonad:
- Mesenchymal (from mesonephros) cells become steroidogenic cell
- Stromal cells (indigenous to medullary region) become fibroblasts, perivascular smooth muscle cells and interstitial ovarian tissue
Preantral to Antral Follicle Transition – Antrum formation
When the follicle reaches a diameter of 200-400µm, surrounded by a vascularized theca, hence subject to circulating influences.
Fluid-filled spaces appear between the granulosa cells which soon coalesce together to form a single, large, fluid-filled cavity or “antrum”.
follicular fluid
fluid formed as exudate of plasma containing secretory products of oocyte & GC
KL and Cx37 are they essential for antrum formation
k/o of these genes result in no antral follicles at all
As the fluid volume increases,
the follicle continues to expand greatly in size.
The Ovarian Follicle structure
Theca externa is
Concentrically arranged smooth muscle cells; innervated by autonomic nerves; lymphatic vessels; important during ovulation
Theca interna are..
Steroid-producing cells; contain LH-r & Insulin-r; richly vascularized
Granulosa cells is invovled in
They differentiate into two mature cell lineages:
involved in endocrine feedback control; express FSHr, P450arom, LHr
GC differentiate into 2 mature cell lineages: mural and cumulus cells.
cumulus oophorus
Remain in contact with oocyte & interact with oocyte via gap junctions; mitotically active; no LHr
COC (cumulus-oocyte complex)
How do they respond so rapidly after LH surge if no LH receptors on cumulus gc?
GC produce:
- EGF-like ligands that bind LH
–>
allow for secretion of hyaluronan and a complex of hyaluronan cross-linking proteins that cause expansion of COC
Inter-cycle rise in FSH crucial for recruitment of AF into the menstrual cycle.
This is crucial for the following reasons: (3)
-Progression of antral follicles
-Selection of dominant follicle
-Fate of remaining AF
In response to LH, theca expresses key
..steroidogenic enzymes to make androgens from cholesterol.
Likewise granulosa cells respond to FSH by up-regulating..
..aromatase (CYP19A1) and 17β-HSD to make oestrogens
Role of FSH in antral follicles
↑ granulosa cell proliferation
↑ aromatase
↑ induce and maintain FSHr
↑ induce and maintain LHr
Interact with paracrine factors