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Ovarian Function Flashcards

1
Q

Until which point in development is formation of the female reproductive system indistinguishable from the male reproductive system?

A

7 weeks (everyone starts off as a lady).

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2
Q

Which stem cells give rise to gametes?

A

Primordial germ cells.

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3
Q

At which point in development do primordial germ cells appear?

Where do they appear?

A
  • Primordial germ cells appear at week 3.

- In the epithelium of the yolk sac.

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4
Q

What happens to primordial germ cells between weeks 3-7 of development?

A
  • 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.
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5
Q

What guides migration of primordial germ cells?

A

Chemotaxis.

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6
Q

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?

A
  • SRY gene.
  • Expressed from week 7 of development.
  • If it is not expressed, female gonad development begins.
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7
Q

From which structures do sex cords arise?

A

Gonadal ridges.

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8
Q

What is the role of the sex cords in female sex development?

A

They cluster around the oogonia and become granulosa cells, forming part of the primordial follicle.

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9
Q

Which structures / cells does the mesonephros give rise to in female sex development?

A

1 - The vasculature of the female reproductive system.

2 - Theca cells.

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10
Q

What sustains female sex development after the 7th week?

A

A lack of endocrine activity that is otherwise present with male sex development.

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11
Q

What happens during female sex development in patients with Turner’s syndrome?

A
  • 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.
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12
Q

List 2 roles of the ovaries post-puberty.

A

1 - To produce mature oocytes.

2 - To produce hormones.

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13
Q

List the stages of development of oocytes from primordial germ cells.

Give the name of the male equivalent cell for each stage.

A

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).

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14
Q

What type of cell division occurs at each stage of female gamete development?

A
  • Mitosis occurs at the primordial germ cell and oogonia stages.
  • Meiosis occurs at the primary and secondary oocytes stages.
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15
Q

List 6 differences between oogenesis and spermatogenesis.

A

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.

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16
Q

How does oogenesis differ from spermatogenesis in the timing of entry into meiosis of the gonadal cells?

A
  • In males, meiosis is initiated post-puberty.

- In females, oogonia enter meiosis during the foetal period (but do not form mature oocytes until puberty).

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17
Q

What controls timing of entry into meiosis in female sex development?

How does male sex development differ?

A
  • 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.
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18
Q

When are the two meiotic blocks during oogenesis?

A

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.

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19
Q

How long can the first meiotic block last?

A

Up to 50 years, until menopause.

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20
Q

What might explain the decrease in female fertility with age?

A

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).

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21
Q

What might explain the higher incidence of chromosomal abnormalities of children born to older women?

A

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.

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22
Q

Why are females born with a finite number of oocytes?

A

It is a consequence of entering into meiosis in utero, depleting the female of stem cells.

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23
Q

What is the greatest number of female germ cells reached during development?

How many will be ovulated?

What happens to the rest?

A
  • 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.
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24
Q

When does clonal expansion occur during female development?

A

During the first month of pregnancy.

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25
Q

List the numbers of germ cells that are present during female development at different stages.

A
  • 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.
26
Q

List 6 signs and symptoms of menopause.

A

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.

27
Q

What is the difference between oligomenorrhoea and amenorrhoea?

A

Oligomenorrhoea is infrequent periods whereas amenorrhoea is a lack of periods.

28
Q

How is menopause defined in the UK?

A
  • 12 months amenorrhoea over 50.

or

  • 24 months amenorrhoea under 50.
29
Q

What hormone replaces oestrogen at menopause?

Which glands are the primary and secondary producers of this hormone?

A
  • Oestrone (a weaker form of oestrogen).
  • The adrenals are the primary producers of oestrone.
  • Adipose tissue is the secondary producer.
30
Q

List 4 consequences of oestrogen withdrawal at menopause.

A

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.

31
Q

How are the symptoms of menopause treated?

A

By hormone replacement therapy, using a combination of synthetic progesterone and oestrogen.

32
Q

Why is progesterone administered to treat symptoms of menopause?

A

Because unopposed oestrogen causes endometrial hyperplasia, so predisposes to endometrial cancer.

33
Q

List 3 risks of hormone replacement therapy for treating symptoms of menopause.

A

1 - Increased risk of breast cancer.

2 - Increased risk of ovarian cancer.

3 - Increased risk of cardiovascular disease.

34
Q

Why do polar bodies form with female oogenesis?

A
  • 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.
35
Q

List the two follicular somatic cells.

A

1 - Granulosa cells.

2 - Theca cells.

36
Q

In which environment are oocytes able to undergo oogenesis?

A

Oogenesis can only occur in follicles.

37
Q

Define primordial follicle.

A

A primary oocyte surrounded by a single layer of flattened granulosa cells.

38
Q

What role does the menstrual cycle have in primary follicle formation?

A

The formation of a primary follicle is independent of the menstrual cycle.

39
Q

List 3 changes that occur during the formation of a primary follicle.

A

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.

40
Q

What is the zona pellucida?

Describe its internal structure.

What is the purpose of its internal structure?

A
  • 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.
41
Q

List 2 functions of the zona pellucida.

A

1 - It is important for sperm binding as it induces the acrosome reaction.

2 - Protection of the early embryo.

42
Q

List 2 changes that occur to an oocyte during the formation of a secondary follicle.

A

1 - Granulosa cells proliferate.

2 - The theca cells form and organise into two distinct layers - interna and externa.

43
Q

How many secondary follicles are produced per menstrual cycle?

A

5-15.

44
Q

List 2 changes that occur to an oocyte during the formation of a tertiary / graafian follicle.

A

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.

45
Q

What is the function of FSH?

How does it carry out its function?

A
  • To stimulate development of follicles at the ovary.

- By binding to the FSHR.

46
Q

What is the function of LH?

How does it carry out its function?

A
  • To stimulate follicle maturation, ovulation and development at the corpus luteum.
  • By binding to the LHCGR.
47
Q

List 5 functions of oestrogens.

A

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.

48
Q

What produces progesterone?

When is progesterone produced?

A
  • The corpus luteum.

- Post-ovulation.

49
Q

What is the function of progesterone?

A

It completes the preparation of and maintains endometrium for pregnancy.

50
Q

What is the two-cell hypothesis for oestrogen production?

A
  • 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.
51
Q

How do FSH and LH affect oestrogen production?

A

They increase oestrogen production:

1 - LH increases cholesterol uptake by the theca.

2 - FSH increases aromatase expression.

52
Q

Describe the feedback mechanisms of oestrogen.

A
  • Moderate levels of oestrogen leads to negative feedback of the pituitary and hypothalamus.
  • High levels of oestrogen leads to positive feedback of the pituitary.
53
Q

Describe the feedback mechanisms of progesterone.

A

Progesterone negatively feeds back to both the hypothalamus and pituitary.

54
Q

Describe the events that occur in the first 4 days of the menstrual cycle.

A

1 - The hypothalamus secretes GnRH, stimulating the pituitary to release FSH.

2 - This stimulates the development of up to 15 follicles.

55
Q

Describe the events that occur in days 5-10 of the menstrual cycle.

A

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’.

56
Q

Describe the events that occur in days 11-14 of the menstrual cycle.

A

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.

57
Q

List the processes that occur during ovulation.

A

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).

58
Q

Describe the events that occur in days 15-23 of the menstrual cycle.

What is this phase known as?

A

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.
59
Q

List the processes that occur if pregnancy occurs following ovulation.

A

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.

60
Q

List the processes that occur if pregnancy does not occur following ovulation.

A
  • 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.
61
Q

List the cells that express FSHR.

A

1 - Granulosa cells.

2 - Testicular Sertoli cells.

62
Q

List the cells that express LHCGR.

A

1 - Granulosa cells.

2 - Theca cells.

3 - Luteal cells.

4 - Testicular Leydig cells.

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