Oogenesis Flashcards
How long is the process of oogenesis?
85 days
What are the phases of oogenesis?
- Proliferative mitosis
- Meiosis
- Cytodifferentiation
How many follicles are present at birth?
2 million
How many follicles are present at puberty?
300 000
How many times will a woman ovulate during her lifetime?
400-450
What are the phases of follicle growth?
- Primordial —- 2. Primary/pre-antral —- 3. Secondary/antral —- 4. Preovulatory
What type of follicle is the Graafian/dominant follicle?
Antral
Which are the type of follicles visible on USS? And why?
Antral - due to the presence of the follicular fluid
What is the size of a primordial follicle?
20 micrometers
What type of oocyte do the primordial follicles contain?
Primary oocytes
From what are the primary oocytes derived?
Primordial germ cells (oogonia), these proliferate during mitosis while the female is a foetus, begin meiosis, again while the female is still a foetus, but cease meiosis at prophase I. It is upon this meiotic block that the oogonia become primary oocytes
When does mitosis occur in females?
While in-utero, i.e. while the female is a foetus
What cells is it that undergo mitosis in females?
Oogonia, i.e. PGCs
When does meiosis begin in females?
While in-utero, i.e. while the female is a foetus
At what point is the first meiotic block/meiotic arrest?
Prophase I
What is the point of the meiotic arrest?
We don’t currently know
At what follicular stage does mitosis and meiosis occur?
Primordial
At what follicular stage are oogonia transformed into primary oocytes?
Primordial
In the primordial follicle, in what is the primary oocyte contained?
Germinal vesicle
What cells surround the germinal vesicle/what cells are contained within the primordial follicle?
Condensed, squamous, granulosa cells
What is the content of the follicle contained within, i.e. what is the BM of the follicle?
Membrana propria
What surrounds the primordial follicles?
Interstitial cells set within the stroma
Which type of cell is homologous to sertoli cells in males?
Granulosa cells
Which type of cell is homologous to leydig cells in males?
Theca cells
At what follicular stage do theca cells not appear until?
Pre-antral/primary
What brings about growth in primordial follicles?
GH mediated by IGF-1, intraovarian cytokines, upon selection t grow into pre-astral/primary follicles
What cells in the follicle produce IGF-1?
Granulosa cells
How many primordial follicles are chosen to grow into pre-astral/primary follicles each day? + what brings about this selection?
A few. It is not clear how these primordial follicles are selected
What is the size of a pre-astral/primary follicle?
200-400 micrometers. The lecture given says the size ‘quadruples’ (clearly at least) compared to a primordial follicle
From what are the theca cells derived?
Formed from stromal cells on the outside of the follicles that condense on the membrane propria
In what order do the theca and granulosa cells proliferate?
Granulosa cell proliferation occurs before theca cell proliferation
At what follicular stage do the granulosa and theca cells proliferate?
Pre-antral/primary
What happens to the granulosa in the pre-antral follicles?
Proliferation, become several layers thick, + become cuboidal (from the squamous shape they were in the primordial follicle)
What shape do the granulosa cells become int he pre-antral follicle?
Cuboidal
At what follicular stage does the primary oocyte reach its ‘final’ diameter?
Pre-antral follicle/primary
What is the ‘final’ diameter of the primary oocyte
60-120 micrometers
In what stage does the cytodifferentiation phase of oogenesis begin?
Pre-antral - remember in oogenesis meiosis and cytodifferentiation take place in tandem
From what is the zona pellucida formed?
Glycoproteins
From where do the glycoproteins that form the zona pellucida come from?
Secreted by the oocyte
From what glycoproteins is the zona pellucida formed?
ZP1; ZP2; ZP3; ZP4
At what follicular stage is the zona pellucida formed?
Pre-antral/primary
What is the thickness of the zona pellucida?
5-10 micrometers
From what does the zona pellucida separate the oocyte from?
Granulosa cells
How is communication/transport maintained between granulosa cells and oocytes, despite the zona pellucida? + why is this maintenance of communication important?
Gap junctions. Important because the oocyte is avascular
At what follicular stage do FSH receptors (only) form? On what cell do the FSH receptors form?
Pre-antral/primary. They form on the granulosa cells?
In summary, what are the differences between primordial and pre-antral follicles?
- Size - growth of both the follicle and primary oocyte
- Theca cell apperance
- Granulosa and theca cell proliferation
- Zona pellucida formation
- FSH receptor formation
What are the type of antral/secondary follicle?
Early and late
At what stage do the theca cells form 2 layers?
Early antral
What are the 2 layers of theca cells?
- Theca externa - a fibrous capsule
2. Theca interna - an inner glandular and highly vascular layer
At what follicular stage is follicular fluid first formed?
Early antral
From what is follicular fluid formed?
- Granulosa cell secretion + 2. Serum transudate
Where does the follicular fluid collect in the early antral follicle?
Between the granulosa cells
What is the follicular antrum?
When droplets of follicular fluid coalesce
What does the appearance of the follicular antrum mark?
The beginning of the antral stage
How many antral follicles are rescued from atresia in each ovary in each menstrual cycle?
7-10 (therefore 14-20 total)
What is atresia?
Oocyte and granulosa cell apoptotic death, leukocyte and macrophage invasion of the follicle and fibrous tissue formation
At what point are the antral follicles rescued int he menstrual cycle?
At the start of each new menstrual cycle
What is it that rescues antral follicles from atresia?
FSH (hence this is the basis of stimulation in IVF - exogenous FSH, Gonal F, is given to increase the number of antral follicles rescued/recruited). Therefore, the theory goes that the antral follicles with the most FSH receptor not heir granulosa cells are the follicles most likely to be recruited
What is the cumulus oopherus?
Layer of granulosa cells that surround the oocyte suspended in the follicular antrum (of follicular fluid)
At what stage does the cumulus oopherus become apparent?
Antral stage
How is an antral follicle selected to become dominant?
Involvement of cytokines, e.g. IGF. And it is FSH that stimulates the availability of IGF for follicular growth, and so a dominant follicle may be more responsive to FSH, i.e. may have more FSH receptors
What are the actions of the dominant follicles?
- Inhibin A production, under action of LH
- Androgen production, also under the action of LH. It is androgens that cause the atresia of the other antral follicles
- Increased aromatase activity in granolas cells - resulting in increased theca androgens being converted to oestrogen. The increase in oestrogen will ultimately bring about the positive feedback needed to bring about the LH surge required for ovulation
Where are LH receptors found?
Theca cells
What happens with regard to LH receptors of the dominant antral follicle?
FSH and the increase in oestrogen cause LH receptors to form on the granulosa cells (not usually found there). Both theca AND granulosa cells need to be able to bind LH in order for the transition from antral to pre-ovulatory follicle to take place
At what point after the LH surge does ovulation occur?
24-36 hours after
What are the 3 changes that LH cause to the pre-ovulatory follicle?
- Causes oocyte expulsion; 2. Causes LH-induced follicular fluid expansion; 3. Changes the whole endocrinology of the follicle
How is the oocyte expelled from the dominant follicle?
- The nuclear membrane disintegrates; 2. The meiotic arrest at PI is reversed, resulting in a secondary oocyte; 3. Cytoplasm maturation occurs within the secondary oocyte
At what meiotic stage is the oocyte upon explosion from the dominant follicle?
MII of meiosis
What are the events involved in the reversal of meiotic arrest?
The oocyte undergoes its first meiotic division in which there is cell division with unequal cytokinesis. One cell receives almost all the cytoplasm - this is the secondary oocyte. The other ‘cell’ is discarded as the 1st polar body (PB). A seance meiotic arrest occurs at MII int he presence of cytostatic factor
What are the events involved in secondary oocyte cytoplasmic maturation?
- The cytoplasmic processes between the oocyte and cumulus oopherus are broken; 2. lysosomal-like granules from he Golgi migrate to the periphery of the oocyte to form the cortical granules; 3. centrioles are lost; 4. new types of proteins are formed
What is the cause of the second meiotic arrest at MII
The presence of a protein complex called cytostatic factor. Cytostatic factor contains c-Mos
From what are the cortical granules derived?
Lysosomal granules from the Golgi
How does LH change the endocrinology of the follicle?
Amortisation is stopped. Granulosa cell begin to produce progesterone instead, under the action of LH on their newly-acquired LH receptors. Granulosa cells stop being able to bind FSH and oestrogen, + instead bind progestins. There is an exponential rise in progesterone in the hours before ovulation as a result
What are the roles of progesterone before the LH surge?
- Depresses the growth of less mature developing follicles; 2. Need for ovulation itself; 3. Used for the transition into the progesterone dominant phase of the ovarian cycle
What is the purpose of the LH-induced follicular fluid expansion int he pre-ovulatory follicle?
Causes the follicle to bulge. The bulging wall = the stigma. The stigma becomes avascular, the tissue break down and the follicle ruptures
What is the corpus luteum?
= the collapsed rupture dominant follicle. Looks like a molluscum on the surface of the ovary
What do the granulosa cells become in the corpus luteum?
Large lutein cells
What do the theca cells become int he corpus luteum?
Small lutein cells
What hormones does the corpus luteum secrete?
- Progesterone; 2. Inhibin A; 3. Oxytocin
What is the action of inhibin A in the corpus luteum?
Promotes progesterone synthesis
When does luteolysis occur?
10-12 days post-ovulation should the woman not become pregnant
What does the corpus luteum form following luteolysis?
Corpus albicans
Why does luteolysis occur?
LH levels falling post-ovulation
