antral folliculogenesis Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

Preantral to Antral Follicle Transition – Formation of Theca is crucial

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Formation and differentiation of theca extremely important for preantral to antral progression. Why?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Theca cells derived from 2 different sources in the embryonic gonad:

A
  • Mesenchymal (from mesonephros) cells become steroidogenic cell
  • Stromal cells (indigenous to medullary region) become fibroblasts, perivascular smooth muscle cells and interstitial ovarian tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Preantral to Antral Follicle Transition – Antrum formation

A

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”.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

follicular fluid

A

fluid formed as exudate of plasma containing secretory products of oocyte & GC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

KL and Cx37 are they essential for antrum formation

A

k/o of these genes result in no antral follicles at all

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

As the fluid volume increases,

A

the follicle continues to expand greatly in size.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

The Ovarian Follicle structure

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Theca externa is

A

Concentrically arranged smooth muscle cells; innervated by autonomic nerves; lymphatic vessels; important during ovulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Theca interna are..

A

Steroid-producing cells; contain LH-r & Insulin-r; richly vascularized

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Granulosa cells is invovled in

They differentiate into two mature cell lineages:

A

involved in endocrine feedback control; express FSHr, P450arom, LHr

GC differentiate into 2 mature cell lineages: mural and cumulus cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

cumulus oophorus

A

Remain in contact with oocyte & interact with oocyte via gap junctions; mitotically active; no LHr

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

COC (cumulus-oocyte complex)

How do they respond so rapidly after LH surge if no LH receptors on cumulus gc?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Inter-cycle rise in FSH crucial for recruitment of AF into the menstrual cycle.

This is crucial for the following reasons: (3)

A

-Progression of antral follicles
-Selection of dominant follicle
-Fate of remaining AF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

In response to LH, theca expresses key

A

..steroidogenic enzymes to make androgens from cholesterol.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Likewise granulosa cells respond to FSH by up-regulating..

A

..aromatase (CYP19A1) and 17β-HSD to make oestrogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Role of FSH in antral follicles

A

↑ granulosa cell proliferation
↑ aromatase
↑ induce and maintain FSHr
↑ induce and maintain LHr

Interact with paracrine factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Autocrine Control of FSHR Expression

A
19
Q

Androgens role in antral follicles

A

Androgens act on granulosa cells (paracrine interaction) to upregulate AR & FSHR

20
Q

AMH role in antral follicles

A

AMH (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

21
Q

Its important to counter-balance effect of AMH, Androgens and FSH to ensure against..

A
  • premature depletion of PF pool and/or
  • premature selection of follicles by FSH
22
Q

Which follicle will be selected (which feature should it have as a bare minimum)

A

follicle with the lowest threshold will be recruited

largest follicle is NOT always selected

23
Q

Factors which assist in dominant follicle selection

A
24
Q

Dominant follicle survives fall in FSH by:

A
  • increased sensitivity to FSH –> increased FSH receptors
  • increased numbers of granulosa cells
  • acquisition of LH receptors
    the LHR gene is switched on by FSH
  • possible involvement of insulin-like growth factors 1&2 (IGF-2 particularly important in humans)
25
Q

DF & IGFs

A

Make this make sense (revise)

26
Q

Importance of LH in folliculogenesis

A
27
Q

Role of LH in Antral Follicles

A

↑ theca function of CYP11a, CYP17
↑ growth & steroidogenesis in dominant follicle
- Withdrawal of gap junctions between gc & oocyte and resumption of meiosis
- Expansion of COC
- Ovulation & luteinization

28
Q

LH signalling in theca interna

A
29
Q

LH and FSH have same 2nd messenger - cAMP
How does the cell distinguish between them?

A
  • FSH produces low cAMP levels
  • LH produces high cAMP levels
30
Q

LH and FSH have same 2nd messenger - cAMP
Role of cAMP apart from signalling?

A
  • provides energy for biosynthetic activity
  • mediates effects of FSH and LH on protein production eg. aromatase, SCC, LHr, proteolytic enzymes
31
Q

Why do we need ovarian angiogenesis?

A

Constant re-modelling to allow for growth of follicle (2-20mm) through the ovarian tissue
- angiogenesis of CL- tissue repair etc.

32
Q

Angiogenic factors are stimulated by primarily

A

primarily by androgens but also oestrogens – theca, gc, stroma all involved

33
Q

Basic fibroblast growth factor (bFGF)

A

endothelial cell mitogen, most potent angiogenic factor

34
Q

Vascular endothelial growth factor (VEGF) (angioigenic factor)

A

endothelial cell mitogen, enhances vascular permeability

35
Q

VEGF-R3

A

Oversees Ovarian lymphatic vessels recruited to theca and stroma layers around growing follicle,

36
Q

Working model for androgen action on endothelial cells:

A

liganded AR (androgen receptor) induces HIF-1 expression which is transcription factor for VEGF

37
Q

AMH secretion is maximal during..

A

small antral follicle stage (≤4mm) and decreases to undetectable levels later

Hence serum AMH reflect small AFs

38
Q

The number of antral follicles (AFC) in the early follicular phase correlates with..

A

numbers of growing follicles only - the ones that have been recruited!

39
Q

Low numbers of antral follicles are a sign of..

A

ovarian ageing

40
Q

Intriguingly, right ovary has been shown to be larger and have higher AFC than left ovary → thought to be due to

A

larger PF pool in right ovary formed in fetal life

41
Q

Premature Ovarian Failure/Primary Ovarian Insufficiency (POI) is defined as and its feature:

A

Defined as ovarian dysfunction <40yrs → oligomenorrhoea or amenorrhoea

Overarching feature is infertility resulting from accelerated depletion or reduced follicle reserve

42
Q

Premature Ovarian Failure/Primary Ovarian Insufficiency (POI)

Aetiology is poorly understood, however this is what we have so far as to causes:

A
  • Environmental genotoxins induce DNA damage eg chemo/radio-therapy for cancer treatment
  • Mutations in genes e.g. BRCA1 and BRCA2that repair DNA double-stand breaks, resulting in diminished ovarian reserve
  • Altered hormonal signalling
  • Chromosomal defects e.g. Turner’s syndrome (XO) → have streak ovaries
  • Autoimmune diseases including thyroiditis & Addison disease
43
Q

To support follicle growth ex-utero, in vitro, two types of environment

A

-Collagen
- Alginate (product of seaweed)

Alginate gels able to produce antral follicles from 2° in monkey & human