S4: Folliculogenesis Flashcards
List the steps of what has to be achieved to reproduce
- Foetus has to differentiate into male or female. 2. Individual needs to sexually mature. 3. Needs to be production, storage and release of sufficient supply of eggs and sperm. 4. There needs to be the correct number of chromosomes in egg and sperm. 5. Eggs and sperm must meet i.e. Gamete transport. 6. The creation of the new individual with genes from both parents. 7. Nurture that child until it is capable of independent life.
Describe primordial germ cells (PGCs) and how they allow gonadal development
- The cells that will become the eggs or sperm originate from the primordial germ cells. - They are first identifiable in the yolk sac of the developing foetus at three weeks post conception. - The PGCs undergo many cycles of mitosis to increase their number and then migrate to the genital ridge in the foetus. - The genital ridge will become the gonad, either testis or an ovary, so further differentiation of the PGCs will depend on whether the gonad develops into testis or ovaries.
Describe what happens when PGCs enter the ovary and become occytes (germ cells to eggs)
- If the genital ridge develops into ovaries, the germ cells will enter into ovary and become oogonia. - The oogonia are egg precursors that are still diploid and increase their numbers by mitosis. The number of oogonia increases drastically up to 7,000,000. - Then, the oogonia stop dividing by mitosis and enter into meiosis and arrest at anaphase in meiosis I. At this stage they are known as primary oocytes and can remain arrested at this phase of meiosis I for a long time until they are ovulated or die. - Primary oocytes can remain arrested for up to 52 years. The longer this is, the higher the risk of aneuploidy. -Subsequently before birth there is a massive loss of primary oocytes by apoptosis, at birth the female will be left with about 500,000 – 1,000,000. Hence a woman has a defined fertility as she has a set number of primary oocytes. - Men are capable of making sperm right up till, they die so they can father children when they’re are very old.
What is the duplication of chromatids?
- Chromosomes replicate during S-phase of cell cycle. - Remain attached at the centromere. - Each copy known as a chromatid and the 2 copies are identical to each other called ‘sister’ chromatids after replication during interphase. - After mitotic division, there are two cells with exact copy of original chromosome.
Overview of mitosis
4 stages: - Prophase - Metaphase - Anaphase - Telophase
Overview of meiosis
Meiosis and mitosis begin the same way. Both are preceded by the replication of chromosomes. - Unlike mitosis, however, meiosis involves two divisions. - In the first division, the chromosome number is reduced, because the two homologues of each pair of chromosomes (each replicated into two chromatids attached by a centromere) are separated into two cells so that each cell has one member of each homologous pair of chromosomes. - In the second division, the replicated chromatids of each chromosome are separated. - We see, then, that meiosis begins with one diploid cell and, two divisions later, produces four haploid cells. - The orderly movements of chromosomes during meiosis ensure that each haploid gamete produced contains one member of each homologous pair of chromosomes. Each of the two meiotic divisions has four stages similar to those in mitosis: prophase, metaphase, anaphase, and telophase. - Proteins responsible for separation of chromosomes can develop mutations and lead to aneuploidy.
Describe oogenesis (divisions of the egg)
- The oogonium starts meiosis and the primary oocyte arrests at meiosis I. - At ovulation it completes meiosis I, the homologues split and oocyte will now be haploid, it contains only one of chromosomes (there are 46 literal chromosomes but 23 are copies of the other, joined by the centromere). - Primary oocytes are packed into the outer layer of the ovary, the cortex.
Describe primary oocytes and primordial follicle (early growth of follicle)
- The oocyte is arrested in the vulnerable meiotic phase for many years therefore each primary oocyte gets surrounded by protective layers of cells that will also nourish it with nutrients it needs to survive. - In the foetal ovary, the surrounding cells condense around the oocyte and differentiate into granulosa cells. - The granulosa cells form a single flattened layer around the occyte (they will later produce steroid). They also secrete an acellular layer called the basal lamina. - The whole structure is called the primordial follicle. There will never be a naked oocyte, they will always be present as follicles.
What happens to the number of primordial follicles before birth?
At birth there is loss of the follicles as the formation of the follicles will sit in a nest and there are lots of follicles not formed properly or naked oocytes in foetus, so these are disposed of before birth. Most die through atresia, a few make it into the menstrual cycle & even less ovulate. The remaining are what females are born with in their ovary (primordial follicle), at puberty there will be growth of these follicles. This is folliculogenesis.
Describe folliculogenesis (pre-antrum - primary follicle)
- Folliculogenesis is defined as the growth and development of follicles from the their earliest “resting” stages as they were laid down in the foetus through to ovulation. - It is important to know that most of the follicles are not growing before puberty and are still at the stage they were made in foetal life. - Once puberty starts, a few (a cohort) grow each day. The follicles grow by multiplication of the granulosa cells, the oocyte itself grows by synthesising protein etc. and as it grows it lays down a thick protective acellular layer called the zona pellucida. This is a sign of growth. This zona pellucida stays attached after ovulation. - Once the cohort of follicles have started growing, there is a second layer of cells that differentiate around the basal lamina, these cells are called the theca. - So the layers of the follicle from outside to inside are now: Theca cells -> Basal lamina -> Granulosa cells -> zona pellucida -> primary oocyte. This is the primary follicle.
Describe folliculogenesis (pre-antrum - secondary follicle)
- So as the follicles (primary) grows, it increases rapidly in diameter and the granulosa cells divisions increase. As this occurs, gaps begin to form between the granulosa cells of the granulosa cell layer.
- Fluid moves through to fill these gaps, to form fluid filled spaces that then combine to form an antrum and are filled with follicular fluid. The oocyte gets pushed to the edge of the cell. This is the antral follicle/secondary follicle.
- The theca layer is now vascularised, it is not influence by anything systemically.
- In the last stage of development of secondary follicle, the granulosa cells are around the fluid filled antrum. Some granulosa cells are specialised and surround the oocyte, these are called the cumulous cells. The whole thing is known as the cumulous oocyte complex.
What are the two phases of follicular growth?
- We use the presence of antrum (fluid filled space) to divide follicular growth into two phases. - The pre-antral phase before the antrum is formed, pre-antral follicle growth is gonadotrophin independent - The antral phase after the antrum is formed, the antral follicles (also called secondary follicles) growth is dependent on gonadotrophins soon after its formation. If there is a lack of gonadotrophins then the follicle will die.
What is needed for post atrum folliculogenesis?
The factors controlling the initiation of growth and the early stages are still largely unknown to science. However, granulosa cells and oocyte enlarges (though still in meiotic arrest). FSH drives most of folliculogenesis but the early growth (multiplication of granulosa cells etc. of the primordial follicle) is independent of FSH and is instead driven by local factors. We know this because: - There are patients who have mutations in FSH or FSH receptor, if you look at their ovaries you still find the early stage growing follicles. - This also means that when FSH is suppressed (e.g. oral contraceptive pill), the follicles will still continue their early growth, but will eventually die as they require FSH to progress. This also means that taking on the OCP doesn’t mean you can preserve your eggs, they still go through early growth. (menopause = when you run out of follicles).
Describe classification of follicles
- Primordial follicle - early growth before folliculogenesis or puberty.
- Preantral/Primary follicle. They are very early and once puberty hits and they start to grow, the granulosa cells will mature to cuboidal (from flattened) and multiply to increase their number. There is no antrum and therefore these are all preantral follicles.
- Antral/Secondary Follicle. This is once the antrum is formed (fluid filled). It is pushing the oocyte (granulosa cells) towards one side. The granulosal cells around the oocyte become specialised into cumulus cells
- Preovulatory/Graafian follicle. This is the mature graafian follicle.
How big is the follicle ready for ovulation?
It can be up to 20 mm in size.
