REPRO: Folliculogenesis

Question 1

What has to be achieved to reproduce?

Answer 1

• differentiation of the foetus into male or female
• sexual maturation
• production, storage and release of sufficient supply of eggs and sperm
• the correct number of chromosomes in eggs and sperm
• eggs and sperm have to meet ie. gamete transport
• creation of a new individual with genes from both parents
• to nurture individual until capable of ‘independent life’

Question 2

Where do egg/sperm cells originate from?

Answer 2

primordial germ cells (PGC).
The PGCs are first identifiable in the yolk sac of the developing foetus at 3 weeks after conception.

They undergo many cycles of mitosis.
They migrate to the genital ridge in the foetus (becoming a gonad).
The further differentiation of the PGC depends on whether the gonad becomes an ovary or testis.

Question 3

The function of the genital ridge

Answer 3

this bipotential cluster of cells becomes either the ovary or testis, which are responsible for the differentiation of PGCs into male/female gametes

Question 4

What happens if primordial germ cells enter the ovary?

Answer 4

PGC’s become oogonia (egg-precusors) when in the ovary.

Oogonia (diploid) and multiply by mitosis.
Once the mitosis stops, they enter and are arrested in meiosis 1 for years -becoming primary oocytes.

At birth, they have been surrounded by a layer of granulosa cells that secrete basal lamina layer (acellular) forming primordial follicles.

ovarian reserve established- females born with the entire stock of primordial follicles

Question 5

How does the primary oocyte become the primordial follicle?

Answer 5

The oocyte will be in its vulnerable first meiotic phase for many years. Therefore, each one becomes surrounded by protective layers and protective cells.

The surrounding cells condense around the oocyte and differentiate into the granulosa cells which secrete the basal lamina layer (acellular)

This whole structure is the primordial follicle.

Question 6

What does the primordial follicle consist of?

Answer 6

primary oocyte + granulosa cells + basal lamina

Question 7

Effect of puberty on primordial follicle

Answer 7

primordial follicles recruited from ovarian reserve and start growing

• some will enter the menstrual cycle and ovulate
• majority of follicles will die through atresia

Question 8

Where do primordial follicles reside before puberty?

Answer 8

they are not growing and rest in the outer cortical layer of the ovary

Question 9

Why are the mitotic divisions of the egg during foetal life critical?

Answer 9

All the eggs that a woman will ever have been made at this stage.

Once the oogonia enter the first stage of meiosis, no more division occurs and they become primary oocytes.

The primary oocyte remains in the first phase of meiosis until it is ovulated (or dies).

Question 10

What is the most immature stage of an ovarian follicle’s development?

Answer 10

primordial follicle

Question 11

What are secondary follicles?

Answer 11

During puberty

• Primary oocyte
• Coated by zona pellucida
• Surrounded by several layers of granulosa cells
• Follicle becomes encased by a new layer of cells called the theca
• Follicular antrum filled with follicular fluid, displacing oocyte to one side

Question 12

Granulosa cells in the antral follicle surrounding the primary oocyte are known as…

Answer 12

cumulus granulosa cells

Question 13

Granulosa cells on the outer structure of the antral follicle are known ass…

Answer 13

mural granulosa cells

Question 14

Briefly describe the splitting of the chromosomes during mitosis.

Answer 14

Interphase
DNA replication forms two sister chromatids, banded together to form a chromosome.

mitosis
sister chromatids separate and move to opposite ends of the cells.

cytokinesis,
parent cell divides, forming two daughter cells. Each daughter cell has two copies of each chromosome (homologous pairs).

Question 15

Briefly describe the splitting of chromosomes during meiosis.

Answer 15

The diploid parent cell contains two homologous pairs of chromosomes.

Interphase
DNA replication forms two copies of each chromosome, and the copies remain attached.

meiosis 1,
homologous chromosomes separate into two haploid cells, each containing one member of each homologous pair.

meiosis 2
sister chromatids separate and four haploid cells are formed that will develop into gametes.

Question 16

Define folliculogenesis.

Answer 16

The growth and development of follicles from the earliest ‘resting’ stages (in foetus) through to ovulation.

Question 17

What regulates follicle growth?

How do we know this?

Answer 17

The factors controlling the initiation of growth are largely unknown.

FSH drives most of the folliculogenesis, but early growth is independent of FSH ie. driven by local factors

• apparent in FSH-deficient patients/ those with mutations of FSHR
• also means that even when FSH is suppressed, eg. on COCP, the follicles will still continue early growth, but then die.

Question 18

Describe follicle growth to form an antrum.

Answer 18

As the follicle starts to grow, it increases rapidly in diameter and granulosa cell divisions increase, but gaps begin to form in the granulosa layers. The gaps consist of fluid-filled spaces which form an antrum and are filled with follicular fluid.

The 2 main phases of follicle growth are labelled by the absence or presence of an antrum. The follicles with an antrum are known as antral or secondary follicles.

Question 19

Describe antral development.

Answer 19

The antrum (the fluid-filled space) expands due to an increase in fluid volume. This causes the oocyte to be displaced to one side.

The oocyte becomes surrounded by cumulus cells, which form the cumulus oophorus, surrounded by the antrum. These cells are very sticky, and they are what the sperm has to fight through to get to the oocyte.

Question 20

what is the first stage of folliculogenesis?

Answer 20

INITIATION (gonadotrophin independent)

• primordial follicles leave ovarian reserve and continuously grow, forming pre-antral follicles
• pre-antral follicles grow until they form early antrum

Question 21

What is the second stage of folliculogenesis?

Answer 21

RECRUITMENT (gonadotrophin dependent)
-follicles will only continue to grow when they reach a size at which they respond to changes in FSH that occur in the menstrual cycle

Question 22

What is the third stage of folliculogenesis?

Answer 22

SELECTION

• follicles respond to FSH and are recruited into the menstrual cycle to continue growing
• only one follicle from the group will be selected for ovulation

Question 23

Describe the 2-cell, 2-gonadotrophin theory/ Function of ovarian follicle

Answer 23

According to the theory, LH stimulates the thecal cells to produce androgens, and FSH stimulates granulosa cells to produce oestrogens from androgens via aromatase.

Question 24

What receptors will granulosa cells acquire? And why?

Answer 24

Granulosa cells of the dominant follicle will acquire LH receptors to respond to the LH surge midcycle and undergo ovulation

Question 25

Control of Folliculogenesis

Answer 25

via the HPO axis:

• GnRH is produced in the hypothalamus
• acts on the anterior pituitary to produce LH and FSH
• FSH and LH act on the ovary to drive antral follicle growth
• antral follicles produce oestrogen and progesterone
• negative feedback on hypothalamus and pituitary to control GnRH and gonadotropin secretion