Antral Folliculogenesis Flashcards
Studies in 1970s showed that when radio-labelled LH/hCG injected into adult female rats localized specifically to the theca layer of small preantral, antral and pre-ovulatory follicles but not primordial follicles
Theca of follicle is envelope of connective tissue, what does it differentiate into?
theca interna & externa containing vascular tissue, immune cells and matrix factors
What is the theca 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
Basically oocyte derived GDF-9 is regulating formation of theca cell layer but not sure if it’s directly/indirectly via other signalling pathways.
How is a theca formed?
Theca cells within the theca layer of growing follicles are derived from two different sources in the embryonic gonad; mesenchymal cells migrating into the ovary from the mesonephros region become the steroidogenic cells, and WT1+ stromal cells indigenous to the embryonic ovarian medullary region become fibroblasts, perivascular smooth muscle cells, and interstitial ovarian tissue, respectively, in the adult ovary
When does the antrum formation switch from preantral to antral follicle transition?
When the follicle reaches a diameter of 200-400µm, surrounded by a vascularized theca, hence subject to circulating influences
How is an antrum formed?
Fluid-filled spaces appear between the granulosa cells which soon coalesce together to form a single, large, fluid-filled cavity or “antrum”
What does the antrum contain?
Contains fluid formed as exudate of plasma containing secretory products of oocyte & GC
Known as follicular fluid
KL and Cx37 essential for antrum formation in lab animals – as k/o of these genes result in no antral follicles at all
What does exudate mean?
Filtered out plasma
As the fluid volume increases the follicle…
continues to expand greatly in size.
Antral follicle range from what sizes?
ranging in size from 0.4-25mm diameter
What is follicular fluid formed of?
Follicular fluid formed by filtration of thecal blood, composition different from plasma as contains secretory products of oocyte and gc
What is the theca externa?
Concentrically arranged smooth muscle cells; innervated by autonomic nerves; lymphatic vessels; important during ovulation
What is the theca interna?
Steroid-producing cells; contain LH-r & Insulin-r; richly vascularized
What does the granulosa cell layer differentiate into?
mural and cumulus cells.
Function of mural granulosa
Mural Granulosa – involved in endocrine feedback control; express FSHr, P450arom, LHr
Function of Cumulus cells
Remain in contact with oocyte & interact with oocyte via gap junctions; mitotically active; no LHr
How do they respond so rapidly after LH surge if no LH receptors on cumulus gc?
GC produce EGF-like ligands that bind LH and allow for secretion of hyaluronan and a complex of hyaluronan cross-linking proteins that cause expansion of COC
In IVF, how is the cumulus layer discarded and oocyte extracted?
Through an enzyme: hyaluronidase
Progression of antral follicles
Selection of dominant follicle
Fate of remaining AF
Inter-cycle rise in FSH crucial for recruitment of AF into the menstrual cycle
**Describe the 2 Cell, 2 Gonadotrophin Concept
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