Follicle development & follicular phase

Question 1

What occurs during folliculogenesis?

Answer 1

• Primordial germ cells migrate from yolk sac & populate gonadal ridge during early foetal development
• gonadal differentiation forms OOGONIA which divide until foetus has high level of germ cells
• germ cells undergo 1st meiotic division then arrest in diplotene of prophase 1 - PRIMARY OOCYTES
• single layer flat granulosa cells surround oocyte to form PRIMORDIAL FOLLICLE

Question 2

What are the different stages of follicular development?

Answer 2

1. Primordial follicle
2. Primary follicle
3. Secondary/pre-antral follicle
4. Antral follicle

Question 3

Describe the formation of primary follicles

Answer 3

• Primordial follicles kept in resting state in primordial follicle pool until signal is given for growth to resume - forms primary follicle
• Recruitment initiated, follicles can never return to resting state - growth continues until follicles become artitic or ovulate
• No response to FSH/LH during/immediately after recruitment
• Pre-granulosa cells -> 1 layer cuboidal GC; dependant on specific growth factors

Question 4

Describe the formation of secondary/pre-antral follicles

Answer 4

• More layers of GC form, acquire FSH receptors
• As follicle grows, GC & surrounding cells secrete proteins that form basement membrane
• Interstitial tissue develops into theca cell layer (interna & externa)
• Theca interna express LH receptors
• Only theca layer has blood vessels
• Can respond to FSH but not dependant on it

Question 5

Describe the formation of antral follicles

Answer 5

• GC & TC proliferation cause antral formation
• Follicular fluid (filtrate thecal blood - steroids, glycosamineglycans, GF, metabolites) collects in antrum
• Growth after antrum formation from fluid accumulation not GC/TC proliferation

Question 6

Describe what happens to the oocyt during follicular development

Answer 6

• Remain arrested in P1 during growth phase
• Grow at same time as follicle from 25μm-110/120μm
• Oocyte attached to luminal GC via cumulus oophorus at opposite pole to ovarian surface
• Communication between oocyte & GC via cytoplasmic processes that penetrate zona forming gap junctions
• meiosis inhibiting factor passed through junctions to keep oocyte in arrested state
• Resume meiosis after early antral phases (species dependant)

Question 7

Describe the role of FSH up until initial antral stages in follicular phase

Answer 7

• Once GC develop FSH receptors they are FSH responsive
• FSH causes mitosis (proliferation of GC, TC) & steroid synthesis
• Follicles can grow until antral stages in rodents & beyond in ruminants in the abscence of FSH
• Follicles never grow beyond initial antral stages if FSH not raised from basal levels - FSH dependant

Question 8

Describe the role of LH up until initial antral stages in follicular phase

Answer 8

• TC differentiate & acquire LH receptors - LH responsive
• LH causes TC proliferation, progesterone & androgen production
• Abscence of LH, follicles will grow up to & beyond initial antral stages of development
• Development of preovulatory follicles & ovulation is LH dependant

Question 9

Describe the role of FSH in follicular phase

Answer 9

• Following antrum formation (rodents)/antral follicles 2-3mm (ruminants), antral follicle growth occurs in a wave-like manner which is initially dependant on elevated [FSH]

1. FSH rises from basal conc. in wave-like manner
2. Cohort follicles acutely FSH dependant, FSH rises cohort emerges
3. Due to follicular secretions (oestradiol & inhibin) [FSH] decreases , follicles become artritic, less & less survive
4. Only dominant follicle survives FSH decline - becomes relatively FSH dependant
5. During dominance period DF secretes oestradiol & inhibin which prevent further FSH rises and follicular waves
6. If DF ovulates/becomes artitic secretions cease, FSH rises, new antral follicle wave develops

Question 10

Describe the role of LH in follicular phase

Answer 10

1. Once cohort selected, continued growth & oestradiol production LH dependant (dependant on frequency of pulses)
2. For further DF/lrg antral follicle survival frequent LH pulses are essential

Question 11

Describe the 2 cell theory of follicular steroidogenesis

Answer 11

1. LH binds to receptors on TC
2. TC uptake cholesterol into mitochondria & convert it to progesterone which is converted to androgens
3. FSH binds to receptors on GC
4. Androgens move into GC & are aromatised to oestrogen & oestradiol

* in sow also happens in TC*

• GC in DF/lrg antral follicles acquire LH receptors - linked to start of progesterone production , enhanced oestradiol production, relative FSH dependance, acute LH dependance

Question 12

What induces the gonadotropin surge at the end of the follicular phase?

Answer 12

• follows the end of the lifespan of a CL
• DF are maximally stimulated by LH to synthesis & secrete lrg amounts of oestradiol
• Abscence of functional CL/progesterone, rapidly increasing oestradiol causes oestradiol feedback on hypothalamus to change from -ve to +ve
• Induces GnRH surge, causes LH & FSH surge
• Responsible for onset of standing heat in ruminants, pig, bitch

Question 13

What changes does the GnRH surge cause to the preovulatory follicle?

Answer 13

• Change in steroid production from oestradiol to progesterone - causes luteinisation
• Synthesis of prostaglandins, oxytocin which are important for ovulation & transformation of oocyte to egg occurs
• Ovulation is an inflammatory process - enzymatic factors weaken follicle wall before ovulation

Question 14

What does the GnRH surge induce in the oocyte?

Answer 14

• germinal vesicle breakdown - nuclear membrane undulates then breaks down
• LH causes gap junctions between cumuls cells & oocyte to deteriorate, inhibitory meiosis factors no longer reach oocyte
• primary oocyte in preovulatory follicle resumes meiosis, reaches metaphase 1, expels 1st polar body & is ovulated in metaphase 2
• oocyte = seconday oocyte & can be fertilised

Question 15

What are the 2 different mechanisms for inducing the GnRH surge at the end of the follicular phase?

Answer 15

1. Spontaneous ovulation - oestradiol rise is in follicular phase after luteal regression, induces GnRH surge & ovulation
2. Induced ovulators - induction of GnRH surge is neuroendocrine reflex initiated by stimulation of vaginal wall/stroking during oestrus

Question 16

Define ‘follicular phase’

Answer 16

Follows regression of the CL. Characterised by enhanced follicle growth and oestradiol production to prepare for the next ovulation. Ends with the next oestrus and ovulation.