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Ovarian Function Flashcards

1
Q

When do males and females become differentiated?

A

Week 7; development is indifferent until then.

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2
Q

What are Primordial germ cells (PGCs) and when do they appear?

A

PGCs give rise to the gametes and appear around week 3.

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3
Q

Outline the action of PGCs in forming the female reproductive system from weeks 3-7.

A

PGCs proliferate by mitosis, migrate by amoeboid movement to the genital ridges, and form the gonads.

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4
Q

What guides migration of PGCs and why is it tightly controlled?

A

Chemotaxis; the dorsal wall and genital ridges secrete factors that attract PGCs. If PGCs get lost, they can cause germ cell cancers.

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5
Q

What experiment was done on mice and what were the results?

A

Godin et al, 1990, showed that in vitro mouse PGCs migrate towards isolated genital ridges in preference to other organs, demonstrating migration via chemotaxis.

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6
Q

When is the SRY gene expressed in males and what does this do?

A

The SRY gene is expressed from week 7 onwards, triggering a cascade of gene expression and protein production that forms the testes.

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7
Q

When does female development occur?

A

Female development occurs in the absence of the Y chromosome at around week 7.

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8
Q

What happens to the genital ridges once PGCs migrate?

A

The same cells are present as in males, but they behave differently, forming primordial follicles instead of tubules.

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9
Q

How do the sex cord cells act differently than they would in a male?

A

They form a cluster around the PGC, resulting in the formation of primordial follicles.

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10
Q

What are oogonia and what do they form?

A

Oogonia are the primordial germ cells surrounded by sex cord cells, which go on to form granulosa cells important for gametogenesis.

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11
Q

What cells form vasculature and what other cells also arrive?

A

Mesonephric cells form the vasculature, and theca cells, the female equivalent of Leydig cells, also arrive.

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12
Q

In terms of endocrine activity, how do females differ from males?

A

There is no endocrine activity during ovarian development in the female fetus, unlike in males.

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13
Q

What is further development of the ovary dependent on?

A

It is dependent on the presence of normal germ cells; both XX chromosomes are needed.

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14
Q

Outline how the development of the female reproductive system varies in Turner syndrome.

A

In Turner syndrome (XO), normal oocyte development requires both X chromosomes, leading to the death of all oocytes and ovarian dysgenesis.

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15
Q

What are the functions of the adult (post-pubertal) ovary?

A

The adult ovary produces oocytes and hormones.

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16
Q

Outline the four main stages of oogenesis.

A
  1. Primordial germ cell – undergoing mitosis. 2. Oogonia – undergoes mitosis. 3. Primary oocytes – undergo 1st meiotic division. 4. Secondary oocytes – undergo 2nd meiotic division.
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17
Q

Compare the female germ cells and male equivalent from start to end.

A
  1. Primordial germ cell – primordial germ cell. 2. Oogonia – spermatagonium. 3. Primary oocytes – primary spermatocyte. 4. Secondary oocytes – secondary spermatocyte. 5. Mature oocyte – spermatozoa.
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18
Q

What are the differences between spermatogenesis and oogenesis?

A
  1. Timing of entry into meiosis. 2. Oogenesis is not continuous. 3. Females are born with a finite number of oocytes. 4. Female germ cells undergo clonal expansion then reduction. 5. Symmetry of meiotic divisions. 6. Females have cyclic gametogenesis.
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19
Q

When do the main differences between spermatogenesis and oogenesis occur?

A

Many of the differences occur in the meiotic phase.

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20
Q

How does timing of entry into meiosis vary in spermatogenesis vs oogenesis?

A

Females: Oogonia enter meiosis during the fetal period, controlled by the Stra8 gene. Males: Meiosis is initiated post-puberty.

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21
Q

How does continuity vary in spermatogenesis vs oogenesis?

A

Males: Spermatogenesis is continuous post-puberty. Females: Oogenesis has a stop-start process with two meiotic blocks.

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22
Q

Describe how meiotic blocks occur in oogenesis.

A

PGCs migrate to genital ridges and form oogonia, which enter meiosis but do not complete it, resulting in primary oocytes arrested at prophase I.

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23
Q

When are the meiotic blocks released?

A

Prophase I arrest is released just before ovulation; metaphase II arrest is released after fertilization.

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24
Q

Describe what happens to primary oocytes after the first meiotic block.

A

Primary oocytes enter a prolonged resting phase lasting up to 50 years, making them vulnerable to damage and leading to a decline in fertility as women age.

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25
How does the number of germ cells vary in spermatogenesis vs oogenesis?
Males can produce sperm until death due to self-renewing spermatogonial stem cells. Females run out of eggs and enter menopause, having all oogonia enter meiosis before birth.
26
Why do female germ cells undergo atresia, when does this occur and why?
Female germ cells undergo clonal expansion then atresia, with massive loss during the first half of pregnancy and continuing throughout adult life for quality control.
27
How does symmetry of meiotic divisions vary in spermatogenesis vs oogenesis?
In males, primary spermatocytes divide symmetrically. In females, division is asymmetric, producing polar bodies.
28
What are polar bodies and their function?
Polar bodies are mechanisms to remove excess genetic material, allowing the mature egg to retain as much cytoplasm as possible for development.
29
What is menopause?
Menopause is amenorrhea for a prolonged time, with an average age of 51 years in the UK.
30
How is a woman classed as menopausal?
A woman is classed as menopausal if she is over 50 and has had 12 months of amenorrhea.
31
What is amenorrhea and its average age in the UK?
Amenorrhea is the absence of menstruation for a prolonged time. The average age is 51 years in the UK.
32
What predominates as a woman transitions to menopause?
As a woman transitions to menopause, oestrone predominates over oestrogen and oestradiol.
33
How is oestrone produced?
Oestrone is produced by the adrenals and adipose tissue, but there is less of it and it is the least potent out of the others.
34
How is a woman classed as menopausal if over 50?
If a woman is over 50, she is classed as menopausal after 12 months of amenorrhea.
35
How is a woman classed as menopausal if under 50?
If a woman is under 50, she is classed as menopausal after 24 months of amenorrhea.
36
How do we detect if a woman is menopausal?
High levels of FSH/LH are how we detect if a woman is menopausal.
37
What is the peri-menopausal/climacteric period?
It is a period of reproductive change that precedes menopause, occurring up to ten years before menopause.
38
What causes the peri-menopausal period?
It is caused by falling oestrogen levels as the body starts to run out of eggs, leading to loss of follicular cells.
39
What happens to FSH/LH levels during the peri-menopausal period?
FSH/LH levels rise as the brain tries to stimulate the ovary.
40
What are common symptoms of menopause/perimenopause?
Symptoms include oligomenorrhea, mood changes, loss of libido, hot flushes, memory problems, vaginal dryness, recurrent UTIs, difficulty sleeping, palpitations, headaches, muscle aches, joint pains, and weight gain.
41
What are the consequences of oestrogen withdrawal?
Consequences include loss of anti-PTH activity leading to osteoporosis, changes in blood lipid ratios increasing coronary thrombosis risk, reduction in vaginal lubrication causing dyspareunia, and behavioral changes like depression and anxiety.
42
What is HRT and its purpose?
HRT (hormone replacement therapy) is used to support women suffering badly during menopause.
43
What does HRT typically consist of?
HRT usually consists of a combination of synthetic progesterone and oestrogen.
44
What is a key consideration for women with a uterus regarding HRT?
Women with a uterus cannot be given oestrogen alone due to the risk of endometrial hyperplasia and cancer.
45
Who can use oestrogen-only HRT?
Oestrogen-only HRT is suitable for women who have had a hysterectomy.
46
What are the risks associated with HRT?
HRT has increased risks of breast and ovarian cancer and cardiovascular disease.
47
Where do oocytes develop?
Oocytes develop within follicles and are supported by somatic cells in the follicles.
48
What are the two types of follicular somatic cells in females?
The two types are granulosa cells, analogous to Sertoli cells in males, and theca cells, analogous to Leydig cells in males.
49
What are the stages of follicular development?
The stages are primordial follicle, primary follicle (pre-antral), secondary follicle (pre-antral), and tertiary follicle (Graafian/antral).
50
Describe the primordial follicle stage in folliculogenesis.
In the foetus, the primary oocyte is surrounded by a single layer of flattened granulosa cells, remaining dormant until puberty. A few primordial follicles begin to grow each day from puberty.
51
Describe the primary follicle stage of folliculogenesis.
The primordial follicle develops into a primary follicle, where the egg grows significantly, granulosa cells become cuboidal, and the theca and zona pellucida become visible.
52
What is the zona pellucida (ZP)?
The ZP is a glycoprotein layer around all mammalian eggs/oocytes, important for sperm binding and protection of the early embryo.
53
Describe the secondary follicle stage of folliculogenesis.
Granulosa cells proliferate, and theca forms two distinct layers. Follicles require FSH to continue developing, with only those at the right stage surviving.
54
Describe the tertiary follicle stage of folliculogenesis.
The tertiary follicle has an antrum, granulosa secretes fluid into it, and the oocyte is surrounded by corona radiata and cumulus cells. Only one dominant follicle develops per cycle.
55
Which stages are dependent on the menstrual cycle?
Development of primordial and primary follicles are independent of the menstrual cycle. Secondary follicles require FSH to continue to develop into tertiary follicles (dependent on menstrual cycle)
56
Outline the Extra-ovarian hormonal action (HPG axis) from puberty.
Hypothalamus secretes GnRH which acts on the Anterior Pituitary. Anterior Pituitary secretes FSH & LH. FSH acts on ovary via FSHR, stimulating development of follicles (secondary → tertiary). LH acts on ovary via LHCGR, stimulating follicle maturation, ovulation, and development of the corpus luteum.
57
What are the functions of ovarian hormones that regulate oogenesis?
Oestrogens promote growth of body and sex organs at puberty, development of secondary sexual characteristics, follicle maturation, preparation of the endometrium for pregnancy, and thinning of cervical mucus. Progesterone, produced by the corpus luteum post-ovulation, completes the preparation of the endometrium for pregnancy and plays key roles during pregnancy.
58
How is oestrogen produced and regulated?
Oestrogen is produced according to the Two-cell hypothesis: Testosterone is produced by theca cells and converted to oestrogen by aromatase in granulosa cells. Regulated by LH increasing cholesterol uptake by the theca and FSH increasing aromatase expression.
59
How do ovarian hormones interact with the HPG axis?
Oestrogen at moderate levels is inhibitory, while at high levels it is stimulatory. Progesterone at high levels inhibits the HPG axis.
60
What are the phases of the menstrual cycle?
The phases of the menstrual cycle are: follicular/proliferation, ovulation, luteal/secretory phase, and pregnancy (maintenance of the corpus luteum) OR luteolysis.
61
Outline the follicular/proliferation phase of the menstrual cycle.
Occurs at the beginning of the month. The hypothalamus secretes GnRH, leading the anterior pituitary to secrete FSH, rescuing and selecting up to 15 follicles for further development.
62
How is oestrogen produced in the FPP and what is its function?
Within the follicles that continue to grow, granulosa and theca cells proliferate, producing oestrogen. Oestrogen thickens the endometrium and thins cervical mucus. Moderate oestrogen suppresses FSH production, allowing one dominant follicle to survive.
63
What happens within the dominant follicle (FPP)?
Granulosa cells in the dominant follicle start expressing LHCG receptor. Oestrogen levels rise, leading to a switch from negative to positive feedback, causing an LH surge from the anterior pituitary.
64
Outline the process of ovulation in the menstrual cycle.
1. Resumption and completion of meiosis I by oocyte. 2. Secondary oocyte enters meiosis II, arresting at metaphase II. 3. Increase in follicular fluid and granulosa cells. 4. Cumulus oophorus stalk loosens. 5. Follicle wall weakens via enzymes. 6. Follicle wall weakness + pressure build-up results in ovulation. 7. Ovulation: the oocyte is released as a cumulus-oocyte-complex. 8. Cumulus-oocyte-complex is picked up by fimbrae of uterine tube. 9. This process takes 30-36 hours from the LH surge.
65
Outline the luteal/secretory phase of the menstrual cycle.
Governed by the corpus luteum, which undergoes luteinisation. Granulosa cells become large lutein cells producing progesterone and oestrogen, while some theca cells remain as small lutein cells. High levels of progesterone and moderate levels of oestrogen provide negative feedback on the HPG axis.
66
What happens to the endometrium under high levels of progesterone (LP)?
The endometrium becomes secretory, producing secretions that support the early embryo while it implants before the placenta forms.
67
How does the ovary detect fertilisation?
The HCG hormone (detected on pregnancy tests) indicates fertilisation.
68
Outline how the uterus lining is maintained and menstruation is prevented during pregnancy.
Syncytiotrophoblast cells of the embryo produce hCG, which binds to LHCGR on lutein cells to maintain the corpus luteum. The corpus luteum produces progesterone and oestrogen to support pregnancy and suppress ovulation. At 6/40 weeks, the placenta takes over, and the corpus luteum degenerates.
69
Outline the luteolysis phase of the menstrual cycle.
If there is no hCG production from an embryo, the corpus luteum degenerates forming the corpus albicans after ~12 days. Progesterone and oestrogen levels fall, removing negative feedback, leading to menstrual shedding.
70
What are the analogues in males and females regarding gametogenesis?
Males: spermatogenesis, spermatogonia, sperm/spermatozoa, Sertoli cells, Leydig cells, primary spermatocyte, secondary spermatocyte. Females: oogenesis, oogonia, egg/oocyte/ovum, granulosa cells, theca cells, primary oocyte, secondary oocyte.
71
How does retinoic acid stimulate meiosis in both males and females?
In females, it increases during the fetal period, activating the Stra8 gene to stimulate meiosis. In males, RA is inhibited pre-puberty, allowing meiosis to continue post-puberty.
72
What roles do LH and FSH play in oestrogen production?
LH increases cholesterol uptake by theca cells, while FSH stimulates granulosa cells to synthesize aromatase, converting androgens to oestrogen. Both hormones increase oestrogen production and drive ovulation.
73
What are the effects of oestrogen and progesterone on the HPG axis?
Oestrogen causes hyperplasia of the endometrium and follicle development; at high levels, it is stimulatory, while at low levels, it is inhibitory of the HPG axis. Progesterone maintains the endometrium and inhibits the HPG axis.

Y2S2M3 (20 decks)

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