Ovarian function Flashcards
Where do the primordial germ cells arise?
From the epiblast of the yolk sac at week 3
How do the PGCs migrate to the gonadal ridges?
Due to amoeboid movement and guided by chemotaixs from the gonadal ridges. As they travel they proliferate. Motility is lost after week 7.
What will result from a loss of PGC migration?
Teratomer
What leads to the development of the female reproductive system?
The absence of Y chromosome leads to the default pathway. Absence of androgens and AMH.
What are the 3 cell types present in the gonadal ridges?
PGCs - oogonia Granulosa cells (somatic) Theca cells (somatic)
Where do the cells develop from?
Sex cord cells cluster around PGCs to form primordial follicles. The sex cords mature into granulosa cells.
Theca cells and vasculature arise from mesenephros.
What is Turner’s syndrome?
xo genotype - oocyte development cannot occur without both x chromosomes. Without germ cells it leads to ovarian dysgenesis (progressive loss of PGCs) and a streak ovary (hypoplastic and fibrous tissue)
What does the development of female organs require?
Absence of androgens and AMH. Normal germ cells for ovary development.
Are post pubertal ovaries homo or heterogeneous?
Heterogeneous as the follicles are all at different stages of development
What is the function of a ovary?
To produce oocytes and hormones
Describe the process through oogenesis.
1) PGCs proliferate through mitosis whilst travelling to ridges
2) Within the ridges oogonia undergo mitosis to produce primary oocyte
3) Primary oocyte undergoes 1st meiotic division to produce secondary oocyte
4) Secondary oocyte undergoes 2nd meiotic division to produce mature tertiary oocyte
When does female meiosis begin and how does it compare to males?
Male begins at puberty.
Female begins during fetal period but is arrested during the same period.
What controls entry into meiosis in both males and females?
Female is controlled via Stra8 (stimulated by retinoic acid 8 gene). Retinoic acid builds in the ovary during fetal development for expression of Stra8.
Males metabolises RA to prevent entry into meiosis before puberty. It is controlled by cytochrome p450.
Where does the first meiotic block occur?
Primary oocyte enters 1st meiosis and is blocked at PROPHASE I. It remains arrested until ovulation.
When does the second meiotic block occur?
On ovulation, meiosis is restarted and completed to produce a secondary oocyte that enters meiosis II, getting blocked at METAPHASE II.
When is meiosis completed?
After fertilisation.
What is the problem with oocytes being arrested?
Makes them vulnerable to damage and fertility declines with age, the longer they are arrested. After 35 years egg quality declines and the risk of trisomy increases due to damage of the spindles needed for chromosomal segregation.
What happens to the number of oocytes throughout life, starting from fertilisation?
Women have a finite number of oocytes as all stem cells enter meiosis before birth. Usually run out around 50yrs.
A fetus has 7 million at 20 weeks but at puberty there is 400,000 but only 500 will be ovulated. Atresia of oocytes begins after 20 weeks gestation due to selection of the best eggs.
What is different about meiotic divisions in females compared to males?
Divisions are asymmetrical, producing polar bodies that contain little cytoplasm and excess genetic material.
When are the polar bodies released?
1st body is released before ovulation on completion of meiosis I. The 2nd body signifies fertilisation and the completion of meiosis II.
Why do polar bodies have little cytoplasm?
Oocytes must compensate for the lack of cytoplasm coming from the sperm, by keeping most of theirs.
Where do oocytes develop within the ovaries?
Within follicles that are supported by the somatic cells, granulosa and theca.
What are the three stages of follicle development?
Primary (preantral)
Secondary (preantral)
Tertiary (Antral / Graafin)
What is a primordial follicle?
A primary oocyte surrounded by a flattened layer of granulosa cells.
What happens to the follicles at puberty?
A few follicles begin to grow each day, taking 365 days to mature to ovulation. As the follicles grow, they synthesis proteins needed for oocyte maturation and the few days post fertilisation. = independent of menstrual cycle
What changes occur in the granulosa cells of a primary follicle?
Become cuboidal
What other changes are noticeable in the primary follicle?
Theca and zona pellucida become visible
What is the zona pellucida?
A glycoprotein layer around the egg with granulosa processes transversing through into the oocyte. It is needed for sperm binding, induction of acrosome reaction and protection of the embryo until implantation.
What changes occur in the secondary follicle?
Granulosa cells proliferate to form a thick layer. Theca cells divide into two layers:
- Interna = endocrine function
- Externa = structure
What is further development after the secondary follicle dependent on?
Previously independent to menstrual cycle but further development requires ENDOCRINE support. This means the follicle must reach the right stage of development at the right time of the cycle for the level of hormones, so only 1 dominant oocyte continues to mature.
What happens to the follicles that do not continue past the secondary follicle?
Undergo atresia and apoptosis
What happens in the tertiary follicle?
It secretes follicular fluid from the granulosa cells into the antrum. The oocyte is surrounded by a layer of corona radiata and a stalk of cumulus cells, both derived from the granulosa cells.
What controls the first half of the menstrual cycle and what controls the final half?
First half controlled by the developing follicle.
Second half controlled by corpus luteum
What is the corpus luteum?
The remnants of the follicle following ovulation
What changes occur in hormone levels at puberty?
Hypothalamus secretes GnRH to act on the anterior pituitary for FSH and LH release.
What is the function of FSH?
Acts on the ovary via FSHR to stimulate the DEVELOPMENT OF FOLLICLES
What is the function of LH?
Acts on the ovary via LHCGR to stimulate FOLLICLE MATURATION, OVULATION and development of corpus luteum.
What hormones does the ovary produce?
Oestrogen
Progesterone
Cytokines
What is the role of oestrogen?
(prepares for fertilisation) Growth of sex organs and characteristics at puberty. Follicle maturation, proliferation of endometrium and thinning of cervical mucus.
What is the role of progesterone?
Produced by corpus luteum post fertilisation. Acts on the uterus to maintain the endometrium and make it receptive for an embryo. Acts in pregnancy.
What cytokines are produced by the ovary?
Inhibin A/B, Activin, GDF9
What is the two cell hypothesis of oestrogen production?
The two somatic cells work together to produce oestrogen.
Theca cells produce testosterone which diffuses to granulosa cells where it is converted to oestrogen by AROMATASE.
What role do LH and FSH have in oestrogen production?
LH increased cholesterol uptake by theca cells to produce more testosterone.
FSH increases aromatase activity for conversion.
What are the feedback mechanisms in the female HPG axis?
High levels of progesterone causes -ve feedback
Oestrogen causes -ve feedback through low levels of inhibin but causes +ve feedback at very high levels. The high levels arise mid-cycle for continued stimulation of follicular maturation.
What are the 3 stages of the menstrual cycle? What does this mean for gametogenesis?
Follicular/Proliferative
Ovulation
Luteal/Secretory
Gametogenesis is cyclic.
What happens during the follicular phase?
Secretion of FSH allows 15 follicles to continue developing, with proliferation of somatic cells.
Oestrogen production causes endometrium to thicken and cervical mucus to thin.
The oestrogen begins to suppress FSH and this creates follicular competition so only one remains.
The oestrogen levels continue to rise as it changes to +ve feedback causing an LH surge. As the granulosa cells express LHCGR it stimulates ovulation.
Describe the ovulation phase.
Oocyte completes meiosis I and arrests in metaphase II. Follicular fluid and granulosa cells increase.
Cumulus stalk loosens and an area in the follicle wall weakens to create a STIGMA, allowing the egg to be released.
The oocyte, ZP and cumulus are released and are picked up by fimbrae 30-36hrs after the LH surge.
What proteins cause the stigma?
MMPs, plasminogen, collagenase, gelatinase
Describe what happens during the luteal phase.
The theca and granulosa cells left behind form the corpus luteum. The cells undergo LUTEINISATION.
Granulosa become large lutein cells that secrete progesterone and oestrogen.
Theca become small lutein cells that secrete progesterone and androgens. The small cells either disperse into stromal tissue or remain to express LHCGR for pregnancy.
Progesterone causes the endometrium to become secretory and receptive for implantation.
This phase causes -ve feedback as the high levels of oestrogen and progesterone suppress LH and FSH.
Why do small cells need to produce androgens?
For aromatisation into oestrogen within the large cells.
What changes occur during pregnancy in regards to the hormones produced?
Trophoblast cells produce hCG which binds at LHCGR on small lutein cells to maintain the corpus luteum for continued progesterone production until the placenta develops.
High levels of oestrogen and progesterone suppress successive ovulations.
At what stage does the placenta take over hormone production?
At week 6. The corpus luteum degrades into corpus albicans before degenerating.
When does hCG production begin?
As it takes 4 days for the embryo to implant, hCG isn’t secreted until day 6. It is vital for development in the first 6 weeks.
What is luteolysis?
After 12 days post ovulation if no hCG is produced, as no implantation occurred successfully, the corpus luteum degenerates in corpus albicans. Progesterone and oestrogen levels fall, removing the -ve feedback so the cycle can commence and the fall in progesterone causes menstruation.
