Folliculogenesis Flashcards
4 things which have to be achieved to reproduce?
Must differentiate into a male or female during embryogenesis
Must sexually mature (undergo puberty)
Must produce, store and release sufficient oocytes or spermatocytes
The gametes must be haploid to prevent aneuploidy at fertilisation
Oocytes or spermatocytes originate from primordial germ cells (PGCs)
They undergo several cycles of mitosis and migrate to genital ridge of fetus, which eventually becomes the gonad
If PGCs enter ovary, they become oogonia
What are oogonia + what do they form?
If PGCs enter ovary, they become oogonia
Oogonia=diploid oocyte precursors, which multiply via several rounds of mitosis
After mitosis, oogonia enter meiosis–> primary oocytes
All the oocytes that a woman will ever have are made at this stage 🤯 therefore the mitotic divisions are critical!
What happens to the oogonia once they enter meiosis?
Aprox how many oocytes are present?
Once the oogonia enter the 1st stage of meiosis, no more division occurs and they become primary oocytes
Primary oocytes can remain in 1st phase of meiosis for up to 52 years (meiotic arrest) until they are ovulated (or die)
There are 5m oocytes 20 weeks of gestation, at birth 500,000 +
Only 50,000 at puberty, of which fewer than 500 are ovulated
Where are primary oocytes packed and what are they protected by?
1° oocytes are packed into the cortex (outer layer) in the ovary. These vital oocytes stay in vulnerable meiotic arrest for many years
Therefore, cells surrounding the 1° oocytes differentiate into granulosa cells, which form a protective basal lamina layer around the oocyte, creating a primordial follicle
All the primordial follicles in the foetal ovary= ‘ovarian reserve’, as females can’t make any more oocytes after embryogenesis
Describe the stages of mitosis for the oogonia
Oogonia undergo mitosis within the ovum:
Prophase: DNA condenses, becoming visible as 2 sister chromatids. The nuclear envelope disintegrates.
Metaphase: Chromosomes line up at the equator, attaching to the spindle fibres
Anaphase: spindles contract, pulling sister chromatids to opposite poles
Telophase: nuclear envelope reforms around the group of chromosomes at each pole of the cell
Cytokinesis: cell divides
compare mitosis vs meiosis
describe meiosis
Meiosis begins the same way as mitosis; chromosomes replicate. Unlike mitosis tho, meiosis involves 2 divisions:
Meiosis I: chromosome number is halved as the 2 homologous pairs of chromosomes separate into 2 diploid cells
Meiosis II: sister chromatids in each cell separate into 4 haploid cells with one of each chromosome (1-22, and X or Y)
Remember that primary oocytes are arrested in meiosis I !!
What is the difference between Oogenesis and folliculogenesis?
What happens post pubertally?
Oogenesis involves the development of egg cells
Folliculogenesis is the formation of ovarian follicles to enclose the oocytes.
The difference between the 2 is that in oogenesis, there is unequal division of the cytoplasm during cytokinesis
Follicles provide support for the naked oocyte- this process occurs after puberty.
Outline 3 things which happen during process of folliculogenesis?
As the follicles start to grow:
- Granulosa cells multiply + become cuboidal shaped
- The oocyte secretes another protective acellular layer called the zona pellucida
- Once follicle growth has started, a 2nd layer of theca cells then differentiate around the existing basal lamina.
This is then vascularised to give the follicle a blood supply
Majority of folliculogenesis is stimulated by FSH- what is the exception to this?
Describe what happens as the follicle grows
What are the 2 main phases of follicular growth?
Early growth= independent of FSH (driven by local factors) - seen in FSH-deficiency or those w FSHr mutations
Also means that even if FSH is suppressed, eg on COCP, follicles still have early growth but then die
As follicle grows, diameter ↑ due to ↑ granulosa cells
Gaps occur between granulosa cells, and fill w/ follicular fluid to form an antrum (fluid joins together)
2 main phases of follicular growth as per antrum formation:
- Follicles w/ no antrum= pre-antral/primary follicles
- Follicles w/ an antrum= antral/secondary follicles
Describe antral follicles in more detail.
What does the follicular fluid consist of?
How do they appear on ultrasound?
Antral follicles contain follicular fluid which is exudate from blood vessels of theca cells
Exudate also contains secretory products of oocyte & GC
As follicular fluid volume & antrum expands, oocyte is displaced to one side
Antral follicles are visible on USS due to this fluid filled antrum. Pre-antral=not US visible
Black space in middle image is follicular fluid (not reflecting sound waves back)
Summarise 3 steps of folliculogenesis.
how long does natural follicle growth take?
Follicle Initiation: A group of early primordial follicles leave resting pool + grow continuously - At a certain point they need FSH to grow further.
Follicle Recruitment: A cohort of early antral follicles will reach the right stage & size that corresponds to the intercycle FSH rise- these antral follicles continue growing
Dominant Follicle selection: only 1 antral follicle selected for ovulation
Remember! natural follicle growth takes 65 days+.
The ovarian follicle produces steroids. Describe the 2-cell-2-gonadotrophin theory
2 steroids produced
According to the 2-cell-2-gonadotrophin theory:
- LH stimulates theca cells to produce androgens, which are taken into the granulosa cells
- FSH then stimulates granulosa cells to produce oestrogens from androgens, via aromatase
- Oestrogen then drives folliculogenesis + goes back into circulation to negatively feedback on the pit. gland
What steroid synthesis pathway is stimulated by granulosa cells?
what can also happen from mid-follicular phase onwards?
In granulosa cells, FSH stimulates aromatase:
Androgens from the theca cells enter granulosa cells, where aromatase converts them to oestrogens (mostly oestradiol, E2) - aromatase gene is only expressed in GCs
Granulosa cells also acquire LHr from the mid-follicular phase (formation of the dominant follicle) onwards:
Now LH can also act on the GCs to also stimulate the delta-4 pathway, –> progesterone production
How many follicles make it to the menstrual cycle?
