Female gametogenesis

Question 1

What are the components of the primordial follicle?

Answer 1

1. Oocyte (containing germinal vesicle)
2. Zona pellucida
3. Granulosa cells

Question 2

What are the stages of follicular development?

Answer 2

1. Primordial follicle
2. Preantral follicle
3. Antral follicle
4. Preovulatory follicle
5. Ovulation
6. Corpus luteum
7. Corpus albicans

Question 3

At what stage is meiosis stalled in the oocyte in the primordial phase?

Answer 3

Prophase I (dictiate stage)

Question 4

What are the changes that occur during the primordial → preantral transition?

Answer 4

1. Growth of the follicle
2. Large amount of protein synthesis
3. Secretion of glycoproteins from oocyte resulting in formation of the zona pellucida
4. Condensation of stroma to form theca

Question 5

What is the endocrine dependence of primordial → preantral transition?

Answer 5

Hormone-independent

Question 6

What is the association between the oocyte and granulosa cells?

Answer 6

Cytoplasmic processes between granulosa cells and oocyte ensure adequate nutritional support

Question 7

What are the changes that occur during preantral → antral transition?

Answer 7

1. Swelling of follicular antrum
2. Oocyte is surrounded by loose layer of granulosa cells called cumulus oophorus
3. A stalk of granulosa cells connect the oocyte to walls of the follicle

Question 8

What is the composition of follicular fluid in follicular antrum?

Answer 8

1. Granulosa cell secretions
2. Serum transudate

Question 9

What is the endocrine dependence of preantral → antral transition?

Answer 9

Hormone dependent

Question 10

What is the endocrine pathway that occurs at preantral → antral transition?

Answer 10

1. Exposure of thecal cells to LH causes increased expression of LH receptors
2. LH stimulates thecal cells to produce androgens
3. Exposure of granulosa cells to FSH causes increased expression of FSH
4. FSH stimulates granulosa cells to convert androgens into oestrogens (oestradiol 17β & oestrone)
5. FSH also stimulates granulosa cells to produce inhibin

Question 11

What are the functions of hormones in follicular development?

Answer 11

1. Both oestrogens and androgens stimulate granulosa cell proliferation and follicular growth
2. Inhibin stimulates thecal cells to produce more androgens

Question 12

What is the structural relation between LH and FSH?

Answer 12

They share homologous α chains but have different β chains

Question 13

What is the structure of LH β chains?

Answer 13

122 amino acids + 2 carbohydrate groups

Question 14

What is the structure of FSH β chains?

Answer 14

111 amino acids + 6 carbohydrate groups

Question 15

What are the +ve feedback loops present in pre-antral → antral transition endocrine pathway?

Answer 15

Oestrogens stimulate granulosa cells to produce more oestrogens

Question 16

What is the follicular selection process during follicular development?

Answer 16

Around 20 follicles enter development at beginning of ovarian cycle but only 1-2 survive to ovulation

Question 17

What is the mechanism behind follicule selection?

Answer 17

1. IGFs are local cytokines that may be a permissive factor in the action of LH and FSH on Thecal and Granulosa cells.
2. Granulosa cells also produce IGF-binding proteins (IGFBPs) that bind to and sequester IGF, preventing them from carrying out their action. This eventually leads to atresia of follicle.
3. FSH inhibits expression of IGFBPs in Granulosa cells and also promotes production of pregnancy-associated plasma protein A (PAPP-A) that cleaves IGF-IGFBP complexes to release IGF.
4. Follicles that have high sensitivity for FSH are better at inhibiting action of IGFBP compared those with lower FSH sensitivity. These follicles are selected for while the others undergo atresia.

Question 18

What is the endocrine regulation of antral → pre-ovulatory transition?

Answer 18

LH surge preceding ovulation

Question 19

What positive feedback loops occur in pre-ovulatory phase?

Answer 19

1. Positive feedback secretion of LH during LH surge
2. Progesterone from granulosa cells stimulate further progesterone secretion

Question 20

What are the changes that occur in the pre-ovulatory follicle?

Answer 20

1. Increased follicular fluid secretion and further swelling of follicular antrum
2. Thecal layer becomes hyperaemic to increase thecal cell androgen synthesis
3. Granulosa cells express LH receptors and respond to LH by producing progesterone

Question 21

What are the changes that occur in pre-ovulatory oocyte?

Answer 21

1. In response to the LH surge, meiosis resumes in the dictyate oocyte, progressing all the way to metaphase II (forming primary oocyte).
2. The primary oocyte undergoes 1^st meiotic division to form:
   - Secondary oocyte
   - 1^st polar body
3. 1^st polar body degenerates
4. Secondary oocyte enters meiosis II.
5. Meiosis once again stalls during metaphase II, and the oocyte is ovulated in this state. Meiosis is completed upon fertilisation.
6. The cytoplasmic processes between the oocyte and Granulosa cells are broken.

Question 22

What is the process of ovulation?

Answer 22

1. Swelling of the follicular antrum results in follicle being surrounded by 1 thin layer of Granuloma cells. The follicle bulges out of the ovarian surface at the point of the stigma.
2. Under influence of several proteases (inc. collagenase & gelatinase), follicle ruptures, releasing oocyte directly into the peritoneal cavity.
3. The oocyte is collected by fimbriae of the oviduct, and enters the fallopian tube.

Question 23

Which hormones are involved in mediating actual release of oocyte from ovaries?

Answer 23

• Progesterone
• Prostaglandins

Question 24

What is the endocrine regulation of formation of corpus luteum?

Answer 24

LH surge

Question 25

What are the components of the corpus luteum?

Answer 25

- Large luteal cells: Derived from Granulosa cells - Small luteal cells: Derived from Thecal cells

Question 26

What is the function of the corpus luteum?

Answer 26

- Large luteal cells: Produce progesterone - Small luteal cells: Produce androgens that are converted to oestrogens in large luteal cells - Secretion of inhibin and oxytocin (probably by large luteal cells)

Question 27

What is the life-span of a corpus luteum?

Answer 27

14 days

Question 28

What is required in order to support the corpus luteum?

Answer 28

LH-like luteotrophic support (i.e. hCG)

Question 29

What is the ovarian cycle?

Answer 29

Time interval between successive ovulations

Question 30

What are the stages in the ovarian cycle?

Answer 30

1. Follicular phase: Dominated by oestrogen secretion from the follicles 2. Ovulation 3. Luteal phase: Dominated by progesterone secretion from the corpus luteum

Question 31

What is the most important oestrogen in control of ovarian cycle?

Answer 31

Oestradiol

Question 32

What are the feedback effects of oestradiol on gonadotrophin secretion from the anterior pituitary?

Answer 32

1. Negative feedback inhibition of gonadotrophin secretion from the pituitary when found in low concentrations in the blood. 2. Positive feedback stimulation of gondadotrophin secretion when high concentrations (~200-400% increase) in blood. This may be responsible for the LH surge responsible for ovulation.

Question 33

From which parts of the hypothalamus to neurones secreting GnRH project?

Answer 33

1. Medial pre-optic nucleus 2. Arcuate nucleus

Question 34

What are the effects of progesterone on gonadotrophin secretion?

Answer 34

Decreases gonadotrophin secretion

Question 35

What are the mechanism by which preogesterone mediates negative feedback control of gonadotrophin secretion?

Answer 35

1. Enhances the negative feedback inhibition of oestradiol on gonadotrophin secretion (direct effect). 2. Inhibits the positive feedback effect of high levels of oestradiol on gonadotrophin secretion (indirect effect).

Question 36

What are the feedback loops present during ovarian cycle?

Answer 36

Question 37

What is the overall endocrine mechanism in control of ovarian cycle?

Answer 37

1. At luteolysis, the levels of corpus luteum-derived oestrogens, progesterone and inhibin A decreases. 2. This relieves the inhibition on gonadotrophin release from the pituitary, causing increase in gonadotrophin release at the beginning of the follicular phase. 3. This allows follicular maturation to occur. 4. Follicular maturation causes increased release of inhibin B and oestrogen. 5. This causes inhibition of gonadotrophin secretion, resulting in plateau in LH and small decline in FSH. 6. As oestrogen levels rise further, positive feedback stimulation of gonadotrophin release occurs, resulting in LH surge that causes ovulation. 7. After ovulation, as the follicles degenerate to become the corpus luteum under the influence of progesterone, oestrogen levels fall and progesterone levels increase. 8. In the luteal phase, oestrogen levels increase as its secretion is restored by corpus luteum. 9. High levels of progesterone inhibit gonadotrophin secretion, even when oestrogen levels rise to those previously able to induce positive feedback stimulation of release. This inhibits further follicular maturation until luteolysis and the beginning of the next follicular phase. 10. If fertilisation occurs, progesterone levels are maintained at high level, inhibiting gonadotrophin release and further follicular maturation.

Question 38

What are the lengths of different stages of ovarian cycle determined by?

Answer 38

1. Follicular phase: Rate of follicular maturation 2. Luteal phase: Lifespan of unsupported corpus luteum

Question 39

What are the mechanisms by which gonadotrophin secretion can be controlled by hormones?

Answer 39

1. Hormones modulate GnRH secretion at level of the hypothalamus 2. Hormones modulate sensitivity of gonadotrophs to GnRH at the level of the anterior pituitary

Question 40

What is the significance of pulsatile nature of GnRH release?

Answer 40

Pulsatile nature of GnRH is essential in maintaining the constant stimulatory effect of GnRH without desensitisation of the gonadotrophs.

Question 41

What evidence is there to suggest that oestorgen acts at level of anterior pituitary to reduce gonadotrophin secretion?

Answer 41

- Hypothalamus is lesioned and replaced with constant pulsatile GnRH - Negative and positive feedback both present when oestradiol administered - Negative feedback present when inhibin administered

Question 42

Why is it unlikely that feedback by oestrogen and inhibin is restricted to the anterior pituitary?

Answer 42

GnRH sensitivity of the anterior pituitary is high during luteal phase despite gonadotrophin secretion being low

Question 43

What are the mechanisms by which feedback control of gonadotrophins is elicited at the level of the hypothalamus?

Answer 43

Oestrogen: - Negative feedback: Oestrogen acts on the arcuate nucleus of the hypothalamus to decrease the amplitude of GnRH pulses. - Positive feedback: Oestrogen acts on the anterior hypothalamus to increase rate of secretion of GnRH from existing neurones or recruit new neurones. Progesterone: - Negative feedback: Progesterone acts on the arcuate nucleus of the hypothalamus to decrease the frequency of GnRH pulses (and blocks oestorgen action on anterior hypothalamus?). Inhibin: Does not act on the hypothalamus

Question 44

What are the effects of oestrogen/progesterone on the fallopian tube?

Answer 44

- Oestrogen in the ovarian cycle aid in maintenance of ciliated epithelium of the fallopian tube, muscular contractions and tubal secretions. - Progesterone has the opposite action and causes decline in number of ciliated epithelial cells, reduced muscular contractions, relaxation of the utero-tubal junction and reduced volume/quality of tubal secretions.

Question 45

What are the effects of oestrogen on the uterus?

Answer 45

- Increased levels of oestrogen in late follicular phase causes: 1. Increased protein synthesis and cellular growth and division in uterine cells 2. Increased excitability and contractility of myometrium 3. Thickening of the endometrial stromal cells 4. Induced expression of progesterone receptors

Question 46

What are the effects of progesterone on the uterus?

Answer 46

Increased levels of progesterone in the luteal phase causes: 1. Increased production of uterine secretions (containing glycoproteins, sugars and amino acids) by uterine glands 2. Further growth of stromal cells 3. Maturation of spiral arteries 4. Further thickening of myometrium but decreased excitability

Question 47

What are the effects of oestrogen/progesterone on the cervix?

Answer 47

- Increased levels of oestrogen during late follicular phase encourages sperm penetration by: 1. Relaxation of cervical musculature 2. Increased secretion of Muc4 and 5B by cervical epithelium - Increased levels of progesterone during the luteal phase discourages sperm penetration by: 1. Contraction of cervical musculature 2. Decreased secretion by cervical epithelium