08 - Folliculogenesis

Question 1

(C. Folliculogenesis)

When we left the fetal ovary, at the end of sex determination:

• The oogonia had finished multiplying by mitosis and were entering into meiosis, becoming oocytes.
• These germ cells had caused the indifferent supporting cells to form granulosa cells which surrounded the oocyte to form a follicle.

Question 2

(C. Folliculogenesis)

(The primordial follicle)

1. Soon after its development the oocyte becomes surrounded by what?

what is this structure called?

2. Primordial follicles recommence growth under what physiological conditions?
3. The reason for initiation of development in the primordial follicle is unknown, a local balance of inhibitory and stimulatory growth factors is involved, but the process is what?

Answer 2

1. a single layer of flattened epithelial cells (precursors to the granulosa cells)

the primordial follicle

2. All physiological conditions and the initiation of development if a continuous process (ie there are always some follicles leaving the resting primordial pool and recommencing development).
3. INDEPENDENT OF GONADOTROPIN SECRETION

Question 3

(Folliculogenesis)

(The primary follicle)

1. With the start of development the surrounding precursor granulosa cells become cuboidal and then do what? beginning formation of what?
2. This change is prolonged…

directed initially by what?

and then what?

3. What appear between the oocyte and the granulosa cells?

Answer 3

1. commence mitosis, formation of the zona pellucida begins
2. the oocyte

a cross-talk between oocyte and granulosa cells using secretion of paracrine factors and direct cell-cell contact

3. gap junctions

Question 4

(Folliculogenesis)

(The primary follicle - cont)

1. The appearance of the zona pellucida (zp) coincides with the initiation of what?
2. The oocyte and its single layer of differentiated (cuboidal) granulosa cells are now termed a what?
3. Receptors for FSH on granulosa cells first appear at primary follicle stage….
   so. .. now dependent on FSH action?

Answer 4

1. oocyte growth
2. primary follicle
3. independent of FSH action

Question 5

(Folliculogenesis)

(The primary follicle)

(The Zona Pellucida)

1. This is a glycoprotein coat, produced by what?
2. It surrounds the oocyte but allows what?

Answer 5

1. by the oocyte from the primary follicle stage onward
2. cellular connections from the cumulus granulosa cells to be maintained

(important role in fertilization)

Question 6

(Folliculogenesis)

(the secondary follicle)

1. As granulosa cells continue to divide more layers are added
2. When the follicle has 2 to 3 layers of granulosa cells in rodents and 4-6 in ruminants… what happens?
3. On reaching the basement membrane surrounding the granulosa, these cells do what?
4. With further mitosis to about four granulosa layers in rodents, the fibrous cell layer is invaded by what?
5. coincident with this, the fibrous cells acquire what and do what?

Answer 6

2. a signal causes migration of another cell type to the outside of the follicle
3. orient parallel to each other to form a fibroblast cell layer around the follicle (that is a precursor to both theca interna and externa)

and the follicle enters the early secondary stage

4. by one or two arterioles which form a network of capillaries adjacent to the basement membrane.
5. LH receptors and begin the differentiation to theca interna and externa

Question 7

(Folliculogenesis)

(The antral or tertiary follicle)

1. What begin to appear between the granulosa cells?

These pools coalesce to from what?

2. There are slight species differences in moving into this stage. For rodents it appears that initial formation of the antrum (transition from secondary to tertiary) requires the actions of both what and what?

How is this different in larger animals?

3. However, continued growth of follicles through the antral stage is FSH-dependent for all species. Because they are now gonadotropin dependent, inadequate FSH support leads what?

Answer 7

1. pools of follicular fluid

the antrum of the small tertiary follicle

2. FSH an oestrogen (ie is FSH DEPENDENT)

In larger animals (ruminants and us) the transition is FSH independent (directed by Gdf9 et al) but FSH-responsive (i.e. you can influence/accelerate it with FSH but it doesn’t need FSH).

3. atresia

Question 8

(Folliculogenesis)

1-3. The granulosa layer of antral follicles is both structurally and functionally heterogenous with at least 3 populations of cells present… what are they?

4. These different sub-populations of granulosa cells have different but cooperative functions. In large follicles the distribution of LH receptors in the granulosa layers is uneven…

which cells in this size have the receptors?

5. (Despite the differences, extensive communications via gap junctions and chemical messengers ensure integrated responses within the granulosa compartment and between it and the oocyte.)

Answer 8

1. mural granulosa cells near follicular basement membrane (most active steroidogenically)
2. antral granulosa cells (line antral cavity)
3. cumulus cells surround oocyte (little or no aromatase activity)
4. mural cells (cumulus and occyte have none)

Question 9

(Graafian follicles)

1. What are these?

Answer 9

1. large mature tertiary follicles (the type you might palpate in a cow or mare)

Question 10

(Stages and Speed of Follicular Growth)

This is basically just another way of looking at the above, but you can divide follicular growth into 3 stages:

(preantral growth phase)

1. covers what time?
2. how fast?

(Tonic growth phase)

1. This phase takes the secondary follicle to what?

(exponential growth phase)

1. A sub-population of follicles (a cohort) are recruited from those at the end of the tonic growth phase (2-5 mm in women) and enter the exponential growth phase that will result in what?

Answer 10

1. time from entry of the primordial follicle into the growing pool until it is a large secondary follicle (ie the period of preantral growth)
2. slow phase of growth
3. a small antral (or tertiary) follicle (FSH responsive in larger spcies)
4. a large, dominant (perhaps ovulatory) follicle (FSH dependent till near end)

Question 11

(Selection)

1. Recruitment resulted in a cohort or pool of similar sized antral follicles
2. While they grow in size, the number of follicles in the cohort is reduced to the species specific ovulatory quota in a process termed what?
3. The process involves both the emergence of the follicle(s) destined to ovulate (dominant follicle of the ovulatory wave) and atresia of the others.

Answer 11

2. selection ((in cows, mares and women this will result in 1-2 ovulatory follicles, in sows it may result in 20).)

Question 12

(Dominance)

1. The mechanism by which one follicle becomes dominant is poorly understood, but the process appears to be under the control of intraovarian factors, especially what system?
2. Within the follicle the actinos of FSH are amplified by what and what?
3. It is currenty thought that within the cohort, one follicle becomes more biochemically advanced (achieves biochemical dominance) than its peers

Answer 12

1. The IGF system
2. estrogen and IGF-1

Question 13

(Dominance - cont)

1. It has been hypothesized that increasing development of this system as the follicle matures enables the dominant follicle to do what?

Increased estradiol (and possibly inhibin) production by this advanced, and other maturing follicles, reduces systemic and intrafollicular FSH levels, doing what?

The higher intrafollicular levels of estrogen and free IGF-1 in the selected follicle means it can do what?

Answer 13

1. to become independent of the systemic (hormonal) environment it is creating

impeding the develpment of less advanced members of the cohort

survive on the reduced FSH support and thus becomes dominant

(essentially these follicles can now use LH in place of FSH)

Question 14

(Follicle Atresia)

1. The vast majority of follicles present on the ovaries at birth degenerate in the process known as what?
2. What percentage of the follicles present in the ovaries at birth will undergo this process?
3. Follicles at all stages of formation are vulnerable, with greatest losses actually occuring when?
4. Atresia is what kind of process?

The fate of an individual follicle depends on what?

5 Appears to first affect what cells?

What appear to control atresia by inducing or suppressing the apoptotic pathway?

What is especially protective for antral follicles?

Answer 14

1. atresia…
2. 99%
3. before birth (involving both oogonia and oocytes)
4. an apoptotic process (ie programmed cell death)

the balance of factors promoting development, gorwth and differentioan vs. those promoting apoptosis

5. granulosa cells (without their support the oocyte dies)

FSH, LH and intraovarian factors

FSH

Question 15

(Patterns of Antral Follicle development during estrous cycle)

1. There is a concept that is being applied to more and more species as they are examined (especially polyestrous species), that growth of antral follicles occurs in waves during the cycle.

(In this scheme…)

1. A cohort of small antral follicles is recruited and does what?
2. Selection is applied and what happens?
3. What arises?

Answer 15

1. grows rapidly (exponential growth phase)
2. some follicles undergo atresia while otehrs continue development
3. The dominant follicle(s)

Question 16

(Patterns of Antral Follicle development during estrous cycle)

(cont)

1. If a dominant follicle develops at a time when it can trigger an LH surge (by its estradiol production when there is no progesterone in the system) what will happen?
2. However, if the follicle becomes dominant when there is still and active CL… what will happen?
3. What will then happen to the follicle?
4. Loss of its suppressive activity allows an increase in FSH secretion and then what happens?
5. Different species may have 1,2,3 or more waves of follicles occuring in an estrous cycle until one of them gives rise to a dominant follicle that can induce ovulation
6. The number of waves per cycle will depend on what?

Answer 16

1. it will ovulate
2. high circulating progesterone levels means it cannot trigger and LH surge
3. it will enter atresia and lose its functional dominance (stop producing estrogen and inhibin).
4. another cohort of small antral follicles commences expoenentrial growth (–> the process repeats…!)
5. the time taken for follicles to grow to ovulatory (or dominant) size, and the length of the luteal phase cycle

Question 17

(D. Patterns of antral follicle development during the estrous cycle)

(cont)

The development of these dominant anovulatory follicles of the luteal phase has been divided into three stages…

1. an active growing phase… where what happens?
2. a static phase, what is this time?
3. A regressing phase, what is this?

During the growth and early static phases the “dominant” follicle is both morphologically (ie largest) and functionally (able to suppress other follicles) dominant, but late in the static phase, while still morphologically dominant, it loses functional dominance permitting emergence of the next wave.

Answer 17

1. the dominant follicle progressively increases in diameter
2. extending from cessation of diameter incrase to commencement of progressive reduction of diameter
3. extending from the end of the static phase until the follicle is no longer detectable.