Folliculogenesis Flashcards
What happens to PGCs in the yolk sac?
Germ cells enter the gonad
Cells that will become eggs or sperm originate from primordial germ cells (PGC)
PGCs first identifiable in the yolk sac of the developing foetus at 3 weeks after conception:
- Undergo many cycles of mitosis
- They migrate to the genital ridge in the foetus
- The genital ridge becomes the gonad
- Further differentiation of the PGC into male/female gametes depend on the sexual differentiation/development of the gonad i.e. into ovary or testis
What happens to PGCs if they enter the ovary?
If PGCs enter the ovary they become oocytes
Germ cells become oogonia when in the ovary
Oogonia are egg-precursors, diploid and multiply by mitosis
Once mitosis stops and they enter into meiosis, known as primary oocytes
Where are primary oocytes located?
Primary oocytes are packed into the outer layer of the ovary known as the cortex
What is the structure of the primordial follicle like?
Oocyte arguably the most important cell in the body and will be in the vulnerable 1st meiotic phase for many years
Therefore each one becomes surrounded by protective layers and cells
In the foetal ovary, the surrounding cells condense around the oocyte and differentiate into the granulosa cells (GC)
The granulosa cells then secrete an acellular layer called the basal lamina (BL)
The whole structure is called the primordial follicle
What happens at the S phase of the cell cycle genetically?
Duplication of chromatids
Chromosomes replicate during S-phase of cell cycle
Remain attached at the centromere
Each copy known as a chromatid → the 2 copies are identical to each other → “sister” chromatids
Exact copy of original chromosomes
What happens to oogonium post-pubertally?
Folliculogenesis and Oogenesis
You have you oogonium and it enters the ovary to become a primary oocyte
At ovulation it will split after its first meiotic division into its two daughter cells but the cytokinesis event is different
There is unequal division of cytoplasm so that one of the daughter cells retains all of the cytoplasm whereas the second daughter cell has just got the chromosome and a very small amount of cytoplasm
That smaller structure created is known as a polar body
At the second miotic division, these other polar bodies might not be produced but what you will get is a mature egg
This process up to primary oocyte is prenatal
The rest is post-pubertal
What is folliculogenesis?
Defined as the growth and development of follicles from the earliest “resting” stages as laid down in the foetus, through to ovulation
Most of the follicles in the ovary are not growing – after puberty a cohort of follicles initiate growth each day
As the follicles start to grow, the granulosa cells (GC) multiply and the oocyte secretes another protective acellular layer called zona pellucida (ZP)
Once growth of the follicles has started a second layer of cells then differentiate around the basal lamina (BL): the theca, which is vascularised
What factors stimulate follicle growth?
The factors controlling initiation of growth and the early stages are largely unknown, but granulosa cells multiply & oocyte enlarges (though still in meiotic arrest)
FSH drives most of folliculogenesis but early growth is independent of FSH i.e. driven by local factors
- Apparent in FSH-deficient patients or those with mutations of FSHr
- Also means that even when FSH is suppressed e.g. on COCP, the follicles will still continue early growth but then die
As follicle starts to grow it increases rapidly in diameter and granulosa cells divisions increase, but gaps begin to form in the granulosa cell layers
These gaps consist of fluid-filled spaces which form an antrum & are filled with follicular fluid
2 main phases of follicle growth labelled by absence or presence of antrum
Follicles with an antrum are known as antral or secondary follicles
What happens to a follicle so that it develops from an antral follicle to a preovulatory one?
The way we go from an antral follicle to a preovulatory/ Graafian follicle
As the fluid filled space expands, all the granulosa cells out to the edge, these are known as mural granulosa cells and the egg remains surrounded by some layers of granulosa cells which have differentiated to become the cumulus cells and attached to the rest by a stalk of granulosa/ cumulus cells
This whole structure (of granulosa cells I’m guessing) is known as the cumulus oophorus complex
You have the vascularised theca laying adjacent to the membrane
What are the characteristics of an antral follicle?
Characterised by a cavity or “antrum”
Contains fluid formed as exudate of plasma containing secretory products of oocyte & GC
Known as “follicular fluid”
As follicular fluid volume and antrum expands, oocyte is displace to one side
What happens during the follicle initiation stage of folliculogenesis?
A cohort of early follicles leaving the resting pool and grow continuously
This is known as follicle initiation
They will NOT continue to grow unless they reach the size at which they respond to changes in FSH that occur in the menstrual cycle
This is known as follicle recruitment
Human pelvis designed in general to carry a single foetus therefore,
- From the group that are recruited only one will subsequently be selected for ovulation
Describe the stage of follicle growth of folliculogenesis?
We have a primordial follicle which initiates growth to form preantral follicles
Preantral follicles consist of multiple layers of granulosa cells, an expanding oocyte, zona pelucida, basal lamina and theca but no antrum
This process can take between two or three months and are gonadotrophin independent
They then start to form a small antrum full of follicular fluid and in order to proceed along they need FSH in a process of recruitment into the menstrual cycle of those who can respond to FSH
They continue to grow and one follicle is selected to become the dominant follicle which will go on to ovulate
The process of growth of the antral cohort of follicles and selection of the ovulatory follicle takes around 15 days in total and coincides with the follicular phase of the menstrual cycle
This stage is completely gonadotrophin dependent as the recruitment process needs FSH and the selection and ovulation process requires LH
What is are the two subsections of the theca?
The theca which we have mentioned previously is divided into two parts the theca interna and the theca externa
The theca interna is adjacent to the granulosa cells and the basement membrane of the follicle
Why is the theca vasculature important?
The granulosa cells are avascular, do they do not have a blood supply
So when the theca forms and starts to develop its own blood supply this means that the follicle is open to influences from the surrounding circulation and also anything the follicle produces can enter the circulation
How does the ovarian follicle produce steroids?
The theca cells will produce androgens, starting from cholesterol
The granulosa cells with take these androgens and convert them into oestradiol
Many of the enzymes responsible for the production of androgens will exist only in the theca cells
Likewise the enzyme most responsible for the conversion form androgens to oestrogens is an aromatase enzyme
Another crucial aspect is that the conversion from androgens to oestrogens is driven by FSH
So FSH binds to its receptor and initiates downstream signalling events which will activate aromatase to do this conversion
But FSH receptors are only found on granulosa cells
Likewise in the theca, the conversion of cholesterol to androgens is driven by LH binding to its receptor and you only find LH receptors in the theca cells (apart from one exception)
