Antral Folliculogenesis Flashcards
(32 cards)
What is formed for the Preantral to Antral Follicle Transition? (3)
Theca:
Theca of follicle is envelope of connective tissue → differentiates
into theca interna &
externa containing vascular tissue, immune cell + matrix factors
- critical for main. structural integrity of follicle + delivering nutrient to avascular GC layer
- Form. and differ. of theca extremely important for
preantral to antral progression.
Theca formation (3)
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 + interstitial ovarian tissue
Antrum formation (3)
follicle reaches a diameter of 200-400μm,
surrounded by a vascularized theca, hence subject to circulating influences.
Fluid-filled spaces appear b/w GC
which soon coalesce together to form a single, large, fluid-filled cavity or “antrum”
- As the fluid volume increases the follicle continues to
expand greatly in size
Antrum (2)
– Contains fluid formed as exudate of plasma containing secretory
products of oocyte & GC
Known as FOLLICULAR FLUID
images
Change in GC & FF volume
As the fluid volume increases, the follicle continues to expand greatly in size.
Ovarian Follicle elements (4)
Theca externa
Theca Interna
GC
Cumulus Oophorus
Theca externa
Concentrically arranged smooth muscle cells; innervated by autonomic nerves; lymphatic vessels;
important during ovulation
Theca interna(3)
Steroid-producing cells;
contain LH-r & Insulin-r;
richly vascularized
GC (3)
Mural Granulosa – involved in endocrine feedback control; express FSHr, P450arom, LHr
Remain in contact with oocyte & interact with oocyte via gap junctions; mitotically active; no 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
How do COC 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 + a complex of hyaluronan cross-linking proteins that cause expansion of COC
Why in the FSH inter-cycle rise important? (4)
crucial for recruitment
of AF into MC
Progression of antral follicles
* Selection of dominant follicle
* Fate of remaining AF
Two-cell, Two-Gonadotrophin Concept (3)
- HPG axis acts to control antral follicle growth at this stage
-In response to LH, theca expresses key steroidogenic enzymes to make androgens from cholesterol.
-GC respond to FSH by up-regulating aromatase
(CYP19A1) and 17β-HSD to make oestrogens
What determines survival of follicles?
FSH:
↑ granulosa cell proliferation
↑ aromatase
↑ induce and maintain FSHr
↑ induce and maintain LHr
Interact with paracrine factors
Autocrine Control of FSHR Expression
image
Androgens + antral Follicles (2)
Androgens act on granulosa cells (paracrine interaction)
to upreg.AR & FSHR
– AR k/o mice have reduced FSHR mRNA
AMH + antral Follicles (4)
(produced by GC of small antral follicles)
acts as a brake on FSH recruitment of antral follicles by:
– decreasing FSH sensitivity
– decreasing FSH-stimulated aromatase expression
Counter-balancing effect of AMH, Androgens and FSH to ensure against.., (2)
– premature depletion of PF pool and/or
– premature selection of follicles by FSH
FSH threshold & DF selection (9)
amount of FSH required to recruit one follicle
»follicle w/ the lowest threshold will be recruited
» largest follicle is not always selected
»FSH receptors
– Increased no,’s
– Coupled more effectively to down-stream signalling
»Growth and Oestradiol production
– increased cell division (2-5 million GC in EFP and 50-100 million at ovulation)
– Size ~5.5-8.2mm in EFP and 18-20mm in LFP
– increased aromatase (200x more E2 than other follicles)
»Androgens & Oestrogens
»Intra-follicular cAMP
»Increased area of theca vasculature
Dominant follicle (5)
Dominant follicle survives fall in FSH by:
»increased sensitivity to FSH = increased FSHr
»increased no. of GC
»acquisition of LHr
‒ the LHR gene is switched on by FSH
»possible involvement of insulin-like growth factors 1&2 (IGF-2 particularly important in humans)
DF & IGFs (bovine)
» IGF-2 enhances FSH effects; stimulates androgen output and
hence oestrogen
» IGF activity suppressed by IGFBP (IGF-binding protein)
» IGF cleaved from IGFBP by PAPP- A (pregnancy-associated plasma
protein A)
» PAPP-A expression high in DF
» Thought that other AF in cohort may have higher levels of IGFBP
hence preventing co-stimulatory effect of IGF & FSH
Importance of LH in folliculogenesis (6)
»inactivating mutations of LH receptor = normal *EFP E2 , anovulatory, multiple cysts, morphologically normal antral follicles
»hypogonadotrophic women:
- FSH treatment effective as long as some LH
present
- E2 is sig.reduced but detectable, why?
* can some A be accessed from adrenal?
»LH k/o mice
* Antral stage growth blocked
Role of LH in Antral Follicles
diagram
LH signalling in theca interna
diagram
