Ovarian Function Flashcards
Until which point in development is formation of the female reproductive system indistinguishable from the male reproductive system?
7 weeks (everyone starts off as a lady).
Which stem cells give rise to gametes?
Primordial germ cells.
At which point in development do primordial germ cells appear?
Where do they appear?
- Primordial germ cells appear at week 3.
- In the epithelium of the yolk sac.
What happens to primordial germ cells between weeks 3-7 of development?
- They proliferate by mitosis.
- They migrate by amoeboid movement to the region of the dorsal wall known as the gonadal ridge.
- Here, they are known as oogonia.
- The structures formed by oogonia are known as primordial follicles.
What guides migration of primordial germ cells?
Chemotaxis.
Which gene is responsible for the initiation of male sex development?
At which stage in development is it expressed?
What happens if it is not expressed?
- SRY gene.
- Expressed from week 7 of development.
- If it is not expressed, female gonad development begins.
From which structures do sex cords arise?
Gonadal ridges.
What is the role of the sex cords in female sex development?
They cluster around the oogonia and become granulosa cells, forming part of the primordial follicle.
Which structures / cells does the mesonephros give rise to in female sex development?
1 - The vasculature of the female reproductive system.
2 - Theca cells.
What sustains female sex development after the 7th week?
A lack of endocrine activity that is otherwise present with male sex development.
What happens during female sex development in patients with Turner’s syndrome?
- Patients with Turner’s syndrome only have one X chromosome.
- Normal oocyte development requires both X chromosomes.
- The lack of a second X chromosome causes oocyte death, which in turn causes ovarian dysgenesis.
- Streak gonads form in place of the ovaries.
List 2 roles of the ovaries post-puberty.
1 - To produce mature oocytes.
2 - To produce hormones.
List the stages of development of oocytes from primordial germ cells.
Give the name of the male equivalent cell for each stage.
1 - Primordial germ cells (same in males).
2 - Oogonia (spermatogonia).
3 - Primary follicle (primary spermatocytes).
4 - Secondary follicle (secondary spermatocytes).
5 - Mature tertiary / graafian follicle (spermatozoa).
What type of cell division occurs at each stage of female gamete development?
- Mitosis occurs at the primordial germ cell and oogonia stages.
- Meiosis occurs at the primary and secondary oocytes stages.
List 6 differences between oogenesis and spermatogenesis.
1 - Timing of entry into meiosis.
2 - Oogenesis is not continuous whereas spermatogenesis is.
3 - Females are born with a finite number of gametes whereas males are not.
4 - Female germ cells undergo clonal expansion then reduction whereas males do not.
5 - Meiotic divisions are asymmetrical in a female, whereas in males they are not.
6 - In females, gametogenesis is cyclic, whereas in males it is not.
How does oogenesis differ from spermatogenesis in the timing of entry into meiosis of the gonadal cells?
- In males, meiosis is initiated post-puberty.
- In females, oogonia enter meiosis during the foetal period (but do not form mature oocytes until puberty).
What controls timing of entry into meiosis in female sex development?
How does male sex development differ?
- The ‘stimulated by retinoic acid 8’ gene (stra8), which is expressed when retinoic acid is high in the gonads.
- Cytochrome P450-mediated metabolism of retinoic acid occurs in males to prevent stra8 expression.
When are the two meiotic blocks during oogenesis?
1 - A primary oocyte is arrested in prophase I in utero.
2 - 1 day before ovulation, meiosis I completes and meiosis II begins.
3 - A secondary oocyte is arrested in metaphase II during ovulation.
4 - Meiosis II completes upon fertilisation.
How long can the first meiotic block last?
Up to 50 years, until menopause.
What might explain the decrease in female fertility with age?
As female germ cells stay in the first meiotic block for so many years, there is a higher probability that they will be damaged by the second meiotic block (ovulation).
What might explain the higher incidence of chromosomal abnormalities of children born to older women?
Since the spindle of the cell is vulnerable to damage, upon reentry of meiosis at the second meiotic block (ovulation), there is a higher probability of problems occurring with chromosomal segregation.
Why are females born with a finite number of oocytes?
It is a consequence of entering into meiosis in utero, depleting the female of stem cells.
What is the greatest number of female germ cells reached during development?
How many will be ovulated?
What happens to the rest?
- 7,000,000 is the greatest number.
- Only 400-500 will be ovulated.
- There is loss of germ cells by apoptosis in a process known as atresia which continues throughout life.
When does clonal expansion occur during female development?
During the first month of pregnancy.
List the numbers of germ cells that are present during female development at different stages.
- At primordial germ cell migration, 170 cells are present.
- At 8 weeks, after clonal expansion begins, there are 600,000.
- This increases to 7,000,000 at 20 weeks, after which atresia begins.
- At birth, 2,000,000 germ cells are present.
- At puberty, 400,000 germ cells are present.
List 6 signs and symptoms of menopause.
1 - Oligomenorrhoea then amenorrhoea.
2 - Mood changes and depression.
3 - Loss of libido.
4 - Hot flushes.
5 - A fall in oestrogen.
6 - A rise in FSH and LH.
What is the difference between oligomenorrhoea and amenorrhoea?
Oligomenorrhoea is infrequent periods whereas amenorrhoea is a lack of periods.
How is menopause defined in the UK?
- 12 months amenorrhoea over 50.
or
- 24 months amenorrhoea under 50.
What hormone replaces oestrogen at menopause?
Which glands are the primary and secondary producers of this hormone?
- Oestrone (a weaker form of oestrogen).
- The adrenals are the primary producers of oestrone.
- Adipose tissue is the secondary producer.
List 4 consequences of oestrogen withdrawal at menopause.
1 - Bone catabolism and osteoporosis due to loss of anti-PTH activity.
2 - Coronary thrombosis due to changes in blood lipid ratios.
3 - Dyspareunia due to a reduction in vaginal lubrication.
4 - Behavioural changes.
How are the symptoms of menopause treated?
By hormone replacement therapy, using a combination of synthetic progesterone and oestrogen.
Why is progesterone administered to treat symptoms of menopause?
Because unopposed oestrogen causes endometrial hyperplasia, so predisposes to endometrial cancer.
List 3 risks of hormone replacement therapy for treating symptoms of menopause.
1 - Increased risk of breast cancer.
2 - Increased risk of ovarian cancer.
3 - Increased risk of cardiovascular disease.
Why do polar bodies form with female oogenesis?
- In the first and second meiotic divisions, only one daughter cell is formed.
- The other product of meiosis is the polar body, which forms because an oocyte undergoing meiosis can’t afford to lose any cytoplasm, so the genetic material is released with a centriole via the polar body.
List the two follicular somatic cells.
1 - Granulosa cells.
2 - Theca cells.
In which environment are oocytes able to undergo oogenesis?
Oogenesis can only occur in follicles.
Define primordial follicle.
A primary oocyte surrounded by a single layer of flattened granulosa cells.
What role does the menstrual cycle have in primary follicle formation?
The formation of a primary follicle is independent of the menstrual cycle.
List 3 changes that occur during the formation of a primary follicle.
1 - Granulosa cells become cuboidal (from flattened).
2 - The theca become visible around the outside of the granulosa cells.
3 - The zona pellucida become visible.
What is the zona pellucida?
Describe its internal structure.
What is the purpose of its internal structure?
- A glycoprotein layer present around all mammalian oocytes.
- It consists of a mesh structure through which granulosa cells send cellular processes that make contact with the oocyte.
List 2 functions of the zona pellucida.
1 - It is important for sperm binding as it induces the acrosome reaction.
2 - Protection of the early embryo.
List 2 changes that occur to an oocyte during the formation of a secondary follicle.
1 - Granulosa cells proliferate.
2 - The theca cells form and organise into two distinct layers - interna and externa.
How many secondary follicles are produced per menstrual cycle?
5-15.
List 2 changes that occur to an oocyte during the formation of a tertiary / graafian follicle.
1 - Granulosa cells secrete a follicular fluid to form the antrum.
2 - Granulosa cells become specialised to form two layers around the zona pellucida known as the cumulus oophorus (a stalk-like structure on the surface) and corona radiata (under the cumulus cells).
3 - The oocyte becomes surrounded by a layer of corona radiata.
What is the function of FSH?
How does it carry out its function?
- To stimulate development of follicles at the ovary.
- By binding to the FSHR.
What is the function of LH?
How does it carry out its function?
- To stimulate follicle maturation, ovulation and development at the corpus luteum.
- By binding to the LHCGR.
List 5 functions of oestrogens.
1 - Growth of body and sex organs at puberty.
2 - Development of secondary sexual characteristics.
3 - Follicle maturation.
4 - Preparation of the endometrium for pregnancy by proliferation of endometrial cells.
5 - Thinning of the cervical mucus.
What produces progesterone?
When is progesterone produced?
- The corpus luteum.
- Post-ovulation.
What is the function of progesterone?
It completes the preparation of and maintains endometrium for pregnancy.
What is the two-cell hypothesis for oestrogen production?
- The hypothesis that both the theca and granulosa cells are required to produce oestrogen:
- Testosterone is produced by theca cells.
- The testosterone diffuses to the granulosa cells where it is converted to oestrogen by aromatase.
How do FSH and LH affect oestrogen production?
They increase oestrogen production:
1 - LH increases cholesterol uptake by the theca.
2 - FSH increases aromatase expression.
Describe the feedback mechanisms of oestrogen.
- Moderate levels of oestrogen leads to negative feedback of the pituitary and hypothalamus.
- High levels of oestrogen leads to positive feedback of the pituitary.
Describe the feedback mechanisms of progesterone.
Progesterone negatively feeds back to both the hypothalamus and pituitary.
Describe the events that occur in the first 4 days of the menstrual cycle.
1 - The hypothalamus secretes GnRH, stimulating the pituitary to release FSH.
2 - This stimulates the development of up to 15 follicles.
Describe the events that occur in days 5-10 of the menstrual cycle.
1 - Granulosa and theca cells develop in growing follicles.
2 - The follicles produce oestrogen, which thickens the endometrium and thins the cervical mucus.
3 - Oestrogen suppresses FSH production. This is the source of selection of follicles since it means no more can develop. The remaining follicle is termed the ‘dominant follicle’.
Describe the events that occur in days 11-14 of the menstrual cycle.
1 - The granulosa cells in the dominant follicle express the LHCG receptor.
2 - High levels of oestrogen mid-cycle (due to positive feedback) causes an LH surge from the anterior pituitary.
3 - LH causes ovulation.
List the processes that occur during ovulation.
1 - Resumption and completion of meiosis I.
2 - The secondary oocyte enters meiosis II and arrests at metaphase.
3 - This is followed by antrum formation and formation of the corona radiata and cumulus cells.
4 - The cumulus oophorus loosens.
5 - The follicle wall weakens due to enzymes such as MMPs, plasminogen, collagenase and gelatinase in the follicle.
6 - When the egg is released, the follicle becomes a corpus luteum (containing the granulosa and theca cells).
Describe the events that occur in days 15-23 of the menstrual cycle.
What is this phase known as?
1 - Negative feedback by high progesterone and oestrogen causes FSH and LH levels to decrease.
2 - The granulosa and theca cells of the corpus luteum undergo a process known as luteinisation:
- The granulosa cells become large lutein cells, and produce progesterone and oestrogen.
- The theca cells become small lutein cells (but many are just dispersed and lost), and produce progesterone and androgens.
3 - The small lutein cells begin to express the LHCGR.
4 - The endometrium becomes secretory.
- This phase is known as the luteal / secretory phase.
List the processes that occur if pregnancy occurs following ovulation.
1 - Trophoblast cells of the embryo produce hCG, which binds to the LHCGR on lutein cells and maintains the corpus luteum.
2 - The corpus luteum produces progesterone and oestrogen to support pregnancy.
3 - Progesterone and oestrogen suppress ovulation.
5 - At 6 weeks of pregnancy, the placenta takes over and the corpus luteum degenerates to form the corpus albicans.
List the processes that occur if pregnancy does not occur following ovulation.
- If there is no hCG production form an embryo within 12 days of ovulation, the corpus luteum degenerates, forming the corpus albicans.
- Progesterone and oestrogen levels fall, removing negative feedback and the cycle recommences.
List the cells that express FSHR.
1 - Granulosa cells.
2 - Testicular Sertoli cells.
List the cells that express LHCGR.
1 - Granulosa cells.
2 - Theca cells.
3 - Luteal cells.
4 - Testicular Leydig cells.
