Folliculogenesis

Question 1

What has to be achieved to reproduce?

Answer 1

• Differentiation into male or female
• Sexual maturation
• Production, storage + release of sufficient eggs + sperm
• Correct number of chromosomes in eggs + sperm (haploid)
• Eggs + sperm have to meet ie. gamete transport
• Creation of new individual with genes from both parents
• To nurture individual until capable of independent life

Question 2

What are primordial germ cells?

Answer 2

Cells that become eggs or sperm

Question 3

When and where are primordial germ cells (PGCs) first identifiable?

Answer 3

• ~ 3 weeks
• In yolk sac of developing foetus

Question 4

What is the general pathway of the PGCs?

Answer 4

• First identifiable in yolk sac
• Undergo many cycles of mitosis
• Migrate to genital ridge in foetus
• Genital ridge -> gonad
• Further differentiation of PGC depending on development of gonad (ie ovary or testis)

Question 5

How do PGCs become oocytes?

Answer 5

• Germ cells migrating + dividing by mitosis
• Germ cells become oogonia when in ovary
• Once mitosis stops, oogonia enter meiosis I + then arrest
• Remain arrested for decades -> these are primary oocytes
• (Upon ovulation they would enter meiosis II)

Question 6

What are oogonia?

Answer 6

Oogonia are egg-precursors, diploid + multiply by mitosis

Question 7

Why are mitotic divisions critical in forming eggs?

Answer 7

All the eggs that a women will ever have are made at this stage

Question 8

Describe duplication of chromatids

Answer 8

• Chromosomes replicate during S-phase of cell cycle (interphase)
• Remain attached at centromere
• Each copy known as a chromatid -> 2 copies identical -> ‘sister chromatids’
• Exact copy of original chromosomes

Question 9

What is a key difference/feature to be noted in oogenesis?

Answer 9

The unequal divsion of cytoplasm during cytokinesis

Question 10

Where are primary oocytes found?

Answer 10

Packed into outer layer of the ovary : the cortex

Question 11

Women are born with the follicle - describe the structure of the primordial follicle within the foetus

Answer 11

• Oocyte becomes surrounded by protective layers/cells
• In foetal ovary, surrounding cells condense around oocyte
• Cells differentiate into the granulosa cells
• The granulosa cells then secrete an acellular layer called basal lamina
• Whole structure is called primordial follicle

Question 12

Define folliculogenesis

Answer 12

Defined as growth and development of follicles from the earliest “resting” stages as laid down in the foetus, through to ovulation.

Question 13

Are follicles in the ovary growing? When do they grow?

Answer 13

Most of the follicles in the ovary are not growing - after puberty only a few grow each day

Question 14

What happens to the structure of the follicle once it starts to grow?

Answer 14

• Granulosa cells multiply + ooctye secretes another protective acellular layer called zona pellucida… which stays attached after ovulation.
• Once growth of follicles has started, a second layer of cells then differentiate around basal lamina: the theca. Theca is vascularised.
• Follicle increases in diameter as granulosa cell divisions increase, gaps form between granulosa cells. Fluid fills these gaps (from theca) to form an antrum.
• Follicles with an antrum are known as antral or secondary follicles.
• Oocyte displaced to one side

Question 15

What is the role of FSH within folliculogenesis?

Answer 15

The factors controlling inititation of follicle growth + early stages are largely unknown.

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

• > apparent in FSH-deficient patients or those w/ mutations of FSHr
• > also means even when FSH suppressed (eg on COCP), the follicles will still continue early growth but then die

Question 16

In which physiological condition would you have low FSH in the reproductive life of a woman?

Answer 16

Pregnancy - already pregnant, don’t want to grow another egg.

Question 17

What are the 3 main, ordered classes of follicles?

Answer 17

• Preantral / primary follicles
• Antral / secondary follicles
• Preovulatory / Graafian follicles

Question 18

What is the role of the zona pellucida?

Answer 18

After one sperm penetrates through it, the rest of the zona pellucida hardens to prevent polyspermy -> this prevent aneuploidy

Question 19

Describe follicle initiation, recruitment and selection

Answer 19

Once puberty established, follicle initiation is where a cohort of early follicles leave the resting pool and grow continuously.

They grow to a certain size but don’t continue unless they get FSH - known as follicle recruitment. At this point they enter into early stage of menstrual cycle.

Only then can one follicle be chosen for ovulation (from the group that was initially recruited) as the human pelvis is designed to carry a single foetus.

Question 20

What is the process called where primordial follicles die?

Answer 20

Atresia - 99.999% die

(‘many follicles to one’)

Question 21

Steroids need to be produced from the follicle itself to survive. Describe the 2-cell, 2-gonadotrophin theory.

Answer 21

According to the 2-cell-2-gonadotrophin theory:

• LH stimulates theca cell receptors -> produce androgens
• FSH stimulates granulosa cell receptors* -> produce oestrogens (from androgens via aromatase)

*FSHreceptors present only in early antral phases on granulosa cells, much later on they begin to express LHreceptors too

Question 22

What are the main features of the steroid production pathway?

Answer 22

• THECA - Sequential removal of Carbon atoms, which will allow for conversion of cholestrol to different subtrates
• Enzymes present in theca cells
• Cholesterol important starting block for all these different products
• Androgens in theca made into estradiol in granulosa (via aromatase)
• At much later stage granulosa cells acquire LHr so can make progesterone from cholesterol