Follicular Phase (lectures 9+10)

Question 1

How does the hypothalamus control GnRH release?

Answer 1

The tonic and surge centres in the hypothalamus control GnRH release. The surge centre responses to high blood concentrations of Estrogen

Question 2

What stuctures govern the the follicular phase?

Answer 2

hypothalamus, anterior pituitary and ovary

Question 3

What segments of the estrous cycle consists of the follicular phase?

Answer 3

proestrus and estus

Question 4

what are the 4 significant events are associated with the follicular phase?

Answer 4

1. Gnrh release from the anterior pituitary (which releases the FSH and LH) after both tonic and surge secretion.
2. follicular preparation for ovulation - follicular growth and reproductive tract preparation
3. Sexual receptivity (oestrus)
4. ovulation

Question 5

What does tonic release control? and how do two hormones in Tnic centers affect GnRH

Answer 5

follicular growth - influenced by progesterone decrease.
neurons in the tonic centre release GnRH slowly over a period of time (episodic profile)

Question 6

How does ovulation occur in relation to hormones?

Answer 6

The surge centre is responsible for Ovulation - releases GnRH that stimulates a surge of LH. Surge centre waits for threshold level of estrogen in the blood, when achieved, large quantities of GnRH is released from terminals in neurons in surge centre. Release of GnRH caused by depolarization from neurosecretory cells.

Question 7

What areas of the hypothalamus is the tonic centre and Surge Centre?

Answer 7

Tonic - ventromedial and arcuate nucleus
Surge - Preoptic and suprachiasmatic nucleus and anterior hypothalamic area

Question 8

What is the relationship between the hypothalamus, the pituitary and ovary during the follicular phase? (mechanism)

Answer 8

Early stage of the follicular phase, GnRH is released from two hypothalamic centres called Tonic and Surge Centres. Tonic centres slowly release GnRH through pulse frequency thus causing FSH and LH to be secreted from the anterior pituitary. FSH and LH are both gonadotropins that stimulate the ovarian follicles to secrete estrogen (estradiol) - creating a positive feedback on the neurons in the hypothalamic surge centred - thus a surge of GnRH occurs. Later in the follicular phase, the follicle secretes inhibin that causes a negative feedback on FSH secretion from the the anterior pituitary.

Question 9

What hormonal changes occur during the follicular phase?

Answer 9

During Proestrus - progesterone drops, FSH and LH increase together in response to GnRH. FSH and LH cause production of estrogen by ovarian follicles.

During Estrus - recruited follicles develop dominance, they produce estrogen and inhibin that suppresses FSH secretion from anterior pituitary. Thus, FSH does not surge with the same magnitude as LH. When estrogen reaches a threshold level the preovulatory surge of LH occurs inducing ovulation.

Question 10

What are the dynamical steps of antral follicles? Go into detail for each step.

Answer 10

1. Recruitment - cohort of small antral follicles are recruited, they grow and produce estrogen and small amounts of inhibin
2. Selection - follicles are selected from recruitment, becoming either atretic or develop. Producing moderate amount of estrogen
3. Dominance - the follicles that did not become atretic become dominant follicles that produce large quantities of estrogen. Dominant follicles will ovulate.

polytocous species will have more than one dominant follicles compared to monotocous species with only one.

Question 11

How many follicular waves occur during one cycle?

Answer 11

Total of 3 waves.

the first two waves occur either during progesterone elevation (metestus) or during peak progesterone production (diestrus) - follicules selected during this period will become atretic.

The last follicular wave after luteolysis) results in dominant follicle that will ovulate. Only those follicles recruited during or after luteolysis will become eligible for ovulation. Follicles from any wave that are in growth phase when luteolysis occurs are capable of ovulation

Question 12

What hormones are associated with the follicular waves?

Answer 12

1. recruitment (entry into gonadotropin sensitive pool) - FSH increases, prompting antral follicle growth
2. selection (ovulatory follicles emerge) - inhibin and estrogen are produced by the follicle and inhibit FSH secretion from the anterior pituitary. Thus the relative roles of LH and FSH begin to shift. FSH secretion is at its lowest point at the time of selection while LH secretion increases
3. Dominance (final growth of ovulatory follicles and inhibition of others) The largest follicles produce large amount of estrogen, prompting preovulatory centre to release a surge of LH. AND, FSH secretion remains low because inhibin and estrogen are secreted in high levels by dominant follicles (believed to cause atresia of other follicles).

Question 13

what percentage does the follicular phase comprise of in the oestrous cycle?

Answer 13

20%

Question 14

When does the follicular phase occur?

Answer 14

continuously throughout the entire cycle, they occur before puberty, during pregnancy, during anoestrus and postpartum. They however do not yield dominant follicles 1st and 2nd wave)

Question 15

Is the process of follicular waves short or long term when compared to pre-antral stages?

Answer 15

short term as primordial oocytes have been sitting waiting in the ovary un nuclea arrest since early embryogenesis.

Question 16

how is estrogen synthesised?

Answer 16

estrogen is synthesis in the antral follicles using two cells. FSH and LH are transported in the blood from the stimulation of GnRH in the anterior pituitary.

1. Hormone -receptor bindin: LH (primary messenger) binds to the target tissue of the theca interna cells of the developing follicle.
2. Adenylate Cyclase Activation: The LH-specific membrane receptors activates adenylate cyclase and G-proteins. This enzyme then converts ATP to cAMP within the cytoplasm of the cell = second messenger.
3. cAMP activates Protein kinases
4. Protein synthesis: Converting cholesterol into testosterone
5. Steroid transportation - Diffuses through the cell membrane using a carrier protein, into the cytoplasm and into the blood.
6. FSH then binds to receptors on the Granulosa Cell, where testosterone has also reach the target cell, and binds to a steroid specific nuclear receptor (transcription factor). Conversion of Testosterone then converts to Estrogen through transcription.
7. The 2-cell 2-gonadotropin model continues until estrogen threshold has been reached and induces the preovulatory LH surge.

Question 17

what are gonadotropin hormones?

Answer 17

FSH an dLH

Question 18

What hormones are released by the posterior pituitary?

Answer 18

Oxytocin and ADH

Question 19

What is the primary target for estrogen?

Answer 19

the reproductive tract -

increases blood flow,
edema of tissues
secretion of mucus
leukocytes
smooth muscle motility
growth of uterine glands

Brain

increase in lordosis (mating posture)
Phonation
Physical activity

Question 20

Can changes in estrogen be detected externally in animals?

Answer 20

yes,
1. mucus secretion from the cervix
2. proliferation of squamous epithelium
3. increased colour and tumescence of the vulval lips
4. vulval winking in the mare

Question 21

What types of ovulation are there in different species?

Answer 21

1. spontaneous - ovulate with a regular frequency and do not require copulation. Ovulation is brought about totally in response to hormonal changes eg. cow, sow, mare, ewe, humans
2. Induced ovulation - stimulation of the vagina and/or cervix for ovulation to occur eg. rabbit, cat, ferret, mink, camelid and koala.

Question 22

What are the ovarian events caused by the preovulatory LH surge?

Answer 22

1. Increase of histamine and prostaglandin (PGE2) causes hyperemia (increased blood flow) and leads to edema (swelling - leaking fluid into the theca interna - surround the follicle) to ovary and dominant follicle. This all increases the follicular pressure.
2. increase in PGR2a (prostaglandin 2 alfa) increases contraction of smooth muscle around ovary and follicle - increase the pressure in follicle. Also releases lysosomal enzymes (particularly from granulosa cells) = leads to wall of follicle becoming weak.
3. LH results in change of hormone production, estrogen was the dominant hormone by the dominant follicle, a shift mediated by surge of LH, causes progesterone results in enzymes called collagenases to increase, which work on the wall to weaken it

page 179 of textbook for diagram.

4. The gap junction breakdown between granulosa cells and oocyte

important for maturing the oocyte the gap junctions start to break down, releasing the changes in the genome of the oocyte.

Removal of meiotic inhibition (they have the oocytes they need in a ovary - they are then inhibited until this point - LH surge causes removal of meiotic inhibition that stopped the development of meiosis) leading to oogenesis, first body develops, haploid body and then fertilization.

Question 23

What part of the Preovulatory LH surge is important for development of the oocyte? Please identify the steps behind this process.

Answer 23

The gap junction breakdown between granulosal cells and ooctye,

1. removal of meiotic inhibition
2. First polar body
3. haploid ooctye
4. fertilization

Question 24

How does induced ovulation work?

Answer 24

Stimulus activates the ovulation of the animal such as a cat.

If stimulation is of sufficient magnitude neurons in the preovulatory centre activate causing large amounts of GnRH to released that stimulates the LH surge.

1. copulation stimulates sensory nerves in the vagina/cervix
2. impulses are then relayed to the spinal cord
3. impulses are then relayed to the surge centre in the hypothalamus

Question 25

What are the four phases of oocyte maturation?

Answer 25

• Mitotic division of primordial germ
  cells – this occurs prenatally in the oocyte going to be available are in the female’s ovary at time of birth - Enter final meiotic stage, to become haploid oocyte, ready for fertilization.
• Nuclear arrest (dictyotene stage ) waiting for cyclicity (nuclear arrest waiting for development) which is cause by LH surge.
• Cytoplasmic growth
• Resumption of meiosis

Question 26

What are the major steps leading to oogenesis?

Answer 26

Female is born with complete supply of germ cells that will supply a future follicular reservoir

The oocyte remains in the first meiotic prophase until stimulated by gonadotropins after puberty - nuclear arrest inactivates the DNA

prior to ovulation the oocyte then grows by increasing in the size of the cytoplasm and zona pellucida forms

once the follicle enters the dominance phase the oocyte is poised to resume meiosis

LH surge and disruption of granulose cells with oocyte removes inhibition on meiosis - occurs before ovulation

IN DOGS AND FOX - meiosis does not occur until after ovulation