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RED > L04 - Ovarian Function > Flashcards

L04 - Ovarian Function Flashcards

1
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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2
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 genital ridge
  • Here, they are known as oogonia
  • The structures formed by oogonia are known as primordial follicles
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3
Q

What guides migration of primordial germ cells?

A

Chemotaxis

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4
Q

What causes the female gonad to develop from week 7 onwards?

A

The absence of a Y chromosome expressing SRY

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5
Q

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

A
  • They cluster around the PGCs (now known as oogonia) to form the primordial follicles
  • Sex cord cells at this point become granulosa cells
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6
Q

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

A

1 - Vasculature

2 - Theca cells

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7
Q

What sustains female sex development after the 7th week?

A
  • There is no endocrine activity during ovarian development in the female foetus, unlike in the male foetus where there is secretion of androgens and AMH
  • Further development of the ovary is dependent on the presence of normal germ cells
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8
Q

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

A
  • Patients with Turner’s syndrome only have one X chromosome (XO)
  • Normal oocyte development requires both X chromosomes
  • The lack of a second X chromosome causes oocyte death
  • Normal ovary development requires normal germ cells
  • The lack of normal germ cells causes ovarian dysgenesis
  • Streak gonads form in place of the ovaries
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9
Q

What are 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 oocyte (primary spermatocytes)

4 - Secondary oocyte (secondary spermatocytes)

5 - Mature / tertiary oocyte (spermatozoa)

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10
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 oocyte stages
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11
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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12
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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13
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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14
Q

When are the two meiotic blocks during oogenesis?

A

1 - A primary oocyte is arrested in prophase I in utero, and can remain at this stage for up to 50 years, until menopause

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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15
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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16
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 re-entry into meiosis at the second meiotic block (ovulation), there is a higher probability of problems occurring with chromosomal segregation

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17
Q

Why are females born with a finite number of oocytes whereas males have infinite spermatozoa numbers?

A
  • Males: spermatogonial stem cells (As spermatogonia) allow renewal

Females: all oogonia enter meiosis before birth so there are no ovarian stem cells

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18
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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19
Q

Why do polar bodies form in female oogenesis?

A
  • The meiotic divisions are asymmetrical, leading to the production of polar bodies
  • These are by-products of meiotic divisions that contain very little cytoplasm & excess genetic material discarded by the egg cell
  • The first polar body is formed before ovulation when the primary oocyte completes meiosis I
  • The second polar body is formed after fertilisation when the secondary oocyte completes meiosis II
20
Q

What are the signs and symptoms of menopause?

A
  • Falling oestrogen
  • Rising FSH/LH
  • Oligomenorrhoea
  • Mood changes – depression
  • Loss of libido
  • Hot flushes
21
Q

How is menopause defined?

A
  • 12 months amenorrhoea (>50yrs)

- 24 months amenorrhoea (<50yrs)

22
Q

Which hormone predominates at menopause and where is it produced?

A
  • Oestrone predominates (less potent)

- Produced by adrenals & adipose tissue

23
Q

What are the consequences of oestrogen withdrawal at menopause?

A
  • Loss of anti-PTH activity, leading to bone catabolism and osteoporosis
  • Change in blood lipid ratios, increasing risk of coronary thrombosis
  • Reduction in vaginal lubrication resulting in dyspareunia
  • Behavioural changes -> ? endocrine, ? psychological
24
Q

How are the symptoms of menopause treated?

A

Hormone replacement therapy (HRT), a combination of synthetic progesterone and oestrogen

25
Q

Why is progesterone administered in addition to oestrogen to treat symptoms of menopause?

A

Unopposed oestrogen can cause endometrial hyperplasia and endometrial cancer

26
Q

What are the risks of hormone replacement therapy for treating symptoms of menopause?

A

Increased risk of:

  • Breast cancer
  • Ovarian cancer
  • CVD
27
Q

What are the two types of follicular somatic cells?

A
  • Granulosa cells (analogous to Sertoli cells)

- Theca cells (similar function to Leydig cells)

28
Q

What is a primordial follicle?

A
  • Forms in the foetus
  • Consists of a dormant primary oocyte surrounded by a single layer of flattened granulosa cells
  • From puberty, a few primordial follicles begin to grow each day, independent of LH and FSH stimulation
  • This process takes up to 375 days but culminates in the formation of a primary follicle
29
Q

What is a primary follicle?

A
  • Every month during puberty, approx. 20 primordial follicles mature into primary follicles
  • Granulosa cells become cuboidal, & theca cells & the zona pellucida become visible
30
Q

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

A

Primary follicle formation occurs independently to the menstrual cycle

31
Q

What is the zona pellucida and what are its functions?

A
  • The zona pellucida is a glycoprotein layer that forms a mesh-like barrier, enabling processes from the granulosa cells to traverse through and maintain contact with the oocyte, essential for oocyte development
  • It is also important for sperm binding, induction of the acrosome reaction & protection of the early embryo
32
Q

What is a secondary follicle?

A
  • The primary follicle forms a secondary follicle through proliferation of the granulosa
  • Approx. 5-15 secondary follicles develop in each menstrual cycle
  • The theca cells form two distinct layers: the hormone-secreting interna and the structural externa
  • This is dependent on the gonadotropin hormones, LH and FSH
33
Q

What is a tertiary follicle?

A
  • One dominant secondary follicle will go on to develop into a tertiary follicle
  • The granulosa cells secrete follicular fluid, forming the antrum
  • The secondary oocyte (which has now completed meiosis I and is in meiosis II) is surrounded by a layer of corona radiata and on a stalk of cumulus cells
34
Q

What is the function of FSH and how does it carry out its function?

A
  • Acts on ovary at FSHR

- Stimulates the development of follicles

35
Q

What is the function of LH and how does it carry out its function?

A
  • Acts on ovary at LHCGR

- Stimulates follicle maturation, ovulation & development of corpus luteum

36
Q

What are the functions of oestrogens?

A
  • Growth of body & sex organs at puberty
  • Development of secondary sexual characteristics
  • Reproduction:

1 - Follicle maturation before ovulation

2 - Preparation of endometrium for pregnancy

3 - Thinning of cervical mucus around ovulation to allow sperm through

37
Q

Where is progesterone produced post-ovulation and what is its function?

A
  • Progesterone is produced by the corpus luteum post-ovulation
  • It acts on the uterus to complete the preparation of the endometrium and maintains it for pregnancy
38
Q

What is the two-cell hypothesis for oestrogen production?

A
  • The theca cells produce testosterone that diffuses to the granulosa
  • Here it is converted to oestrogen by the enzyme aromatase
39
Q

How do FSH and LH affect oestrogen production?

A
  • LH increases cholesterol uptake by theca cells

- FSH increases aromatase expression

40
Q

Describe the feedback mechanisms of progesterone.

A

Negative feedback occurs from progesterone to the pituitary and hypothalamus to lower levels of LH and FSH

41
Q

Describe the feedback mechanisms of oestrogen.

A
  • Negative feedback occurs from oestrogen to the pituitary and hypothalamus to lower levels of LH and FSH
  • However, high levels of oestrogen mid-cycle result in the stimulation of LH and FSH secretion from the pituitary
42
Q

What events occur in the follicular/proliferative phase of the menstrual cycle?

A
  • Hypothalamus secretes GnRH and the anterior pituitary secretes FSH + small amounts of LH
  • FSH ‘rescues’ up to 15 primary follicles from atresia and their theca & granulosa cells develop, forming a secondary follicle
  • The theca produce testosterone which is aromatised to oestrogen in the granulosa
  • Oestrogen thickens the endometrium and thins the cervical mucus, and suppresses FSH production by the anterior pituitary through negative feedback
  • This FSH reduction allows selection of the dominant follicle to become a tertiary follicle
  • Granulosa in the dominant follicle express the LHCG receptor and proliferate to produce increasing levels of oestrogen
  • High levels of oestrogen mid-cycle cross threshold and cause an LH surge
43
Q

What events occur in the ovulation phase of the menstrual cycle?

A
  • Primary oocyte within the dominant follicle will resume meiosis I & resultant secondary oocyte will enter meiosis II before arresting at metaphase
  • Increase in follicular fluid & the number of granulosa cells, forming a tertiary follicle
  • Cumulus oophorus loosens & follicle wall weakens at the stigma (surface where tertiary follicle will burst)
  • Ovulation - the release of the cumulus-oocyte complex
  • Cumulus-oocyte complex is picked up by fimbriae of the fallopian tube
44
Q

What events occur in the luteal/secretory phase of the menstrual cycle?

A
  • The corpus luteum is produced by the follicle from which ovulation has just occurred
  • Granulosa cells form large lutein cells that secrete oestrogen and progesterone
  • Many theca cells disperse to the stromal tissue, but those that remain in the corpus luteum form small luteal cells that secrete progesterone and androgens (that are aromatised to oestrogens in the large luteal cells)
  • Negative feedback then occurs to lower LH and FSH levels in response to high progesterone and moderate (below threshold) oestrogen
45
Q

What processes occur if the oocyte is fertilised following ovulation?

A
  • Trophoblast cells of embryo produce hCG, which binds to LHCGR on small lutein cells to maintain corpus luteum
  • Corpus luteum continues to secrete progesterone until week 6
  • After week 6, the placenta takes over & corpus luteum degenerates into the corpus albicans
  • Oestrogen & progesterone levels suppress ovulation via negative HPG feedback
46
Q

What processes occur if the oocyte is not fertilised following ovulation?

A
  • Luteolysis occurs if there is no hCG production after approx. 12 days post-ovulation
  • Corpus luteum degenerates into corpus albicans
  • Progesterone & oestrogen levels fall, removing the negative feedback on the HPG axis, and recommencing the cycle

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