5. THE MENSTRUAL CYCLE

Question 1

What are the aims of the menstrual cycle?

Answer 1

1. Selection a single oocyte
2. Preparation of the uterus
3. Correct number of chromosomes in an egg e.g haploid
4. Regular spontaneous ovulation
5. Support of the fertilised egg

Question 2

What are the two phases of the menstrual cycle which is separated by ovulation?

Answer 2

1. FOLLICULAR PHASE
2. LUTEAL PHASE
   - The follicular & luteal phase are separated by ovulation

Question 3

What is the follicular phase?

Answer 3

• Menses is the first 5 days of the early follicular phase where a decline in progesterone causes a rise in FSH. The rise in FSH is needed for the growth of the follicles
• The follicular phase is dominated by oestrogen
• It involves the development of a follicle & the selection of a dominant follicle
• Oestrogen is produced by the granulosa cells, a rise in oestrogen then causes a drop in FSH
• The follicular phase is

Question 4

What is he luteal phase?

Answer 4

• The luteal phase occurs after ovulation & is dominated by progesterone
• Ovulation releases the secondary oocyte & the remainder of the follicle forms the corpus luteum.
• The corpus luteum is made up of luteinised theca & granulosa cells which produce progesterone
• The corpus luteum has a finite lifespan of 14 days, so the luteal phase is always 14 days before the beginning of the next cycle

Question 5

When does ovulation occur?

Answer 5

• Ovulation occurs at the end of the follicular phase
• The ovarian follicle ruptures & the secondary oocyte is released into the fallopian tubes
• Ovulation is said to occur at the middle of the cycle, but the day depends on the length of the follicular phase

Question 6

Describe HPG axis feedback for the luteal phase

Answer 6

• During the luteal phase, the levels of progesterone are high
• High levels of progesterone result in negative feedback, so the levels of FSH & LH decline

Question 7

Describe the HPG axis feedback for the follicular phase

Answer 7

1. Early follicular - menstruation occurs due to a decline in progesterone, the low levels of progesterone cause FSH & LH to rise, so there’s a release of negative feedback. The inter-cycle rise in FSH is also needed for the growth of the follicles
2. Negative feedback reinstated - the follicles continue to grow as FSH rises, but oestrogen levels rise due to E2 production from granulosa cells. The increase in oestrogen causes negative feedback so FSH drops. Drop in FSH helps select dominant follicle
3. Positive feedback - Oestrogen levels steadily increase, reach 300pmol which switches negative -> positive feedback. FSH & LH begin to rise mid-cycle

Question 8

What are the different stages of the menstrual cycle?

Answer 8

1. Early follicular
2. Mid-follicular
3. Mid-cycle/ovulation
4. Mid - luteal/ late luteal

Question 9

What happens in the early follicular phase?

Answer 9

• In the early follicular phase, progesterone levels are low which triggers menses (breakdown of endometrial lining)
• The decline in progesterone causes negative feedback where the FSH levels rise, known as the inter-cycle rise in FSH
• Inter-cycle rise in FSH is needed for the growth of follicles

Question 10

What happens in the mid-follicular phase?

Answer 10

• As the follicles grow due to FSH, oestrogen production increases due to granulosa cells
• Increase in oestrogen causes negative feedback, leading to a drop in FSH
• The fall in FSH allows a dominant follicle to be selected. Only the follicle that expresses the most amount of FSHr will survive the drop in FSH, the others will die & this follicle will be the dominant follicle

Question 11

What happens in the mid-cycle/ovulation phase>

Answer 11

• Oestrogen steadily increases until it reaches 300pmol, switching the negative feedback to positive
• An increase in oestrogen then results in an LH surge
• This LH surge causes the primary oocyte to resume the first meiotic division, forming a secondary oocyte
• The secondary oocyte is arrested in Meiosis II & is released into the fallopian tube when the ovarian follicle ruptures. This process is known as ovulation
• The LH surge is responsible for triggering ovulation

Question 12

What happens in the mid-luteal & late luteal phase?

Answer 12

• Once ovulation has occurred, teh remainder of the follicle will form teh corpus luteum which is made up of luteinised theca & granulosa cells
• The corpus luteum produces progesterone which leads to a drop in FSH & LH
• Oestrogen is still produced but progesterone overcome the levels
• If fertilisation doesn’t occur, the corpus luteum will degenerate to form the corpus albicans.
• The prigesterone levels will begin to decline as the corpus luteum degenerates, triggering menses in the next cycle

Question 13

What’s the importance of the inter-cycle rise & fall of FSH?

Answer 13

• inter-cycle rise FSH = allows for growth of follicles. Allows follicles to get to right size & stage before selection
• inter cycle fall FSH - allows selection of dominant follicle, only folllicle with the most FSHr will survive the drop in FSH & the others will die

Question 14

How do dominant follicle survive the fall in FSH?

Answer 14

1. Increased sensitivity to FSH
2. Increased FSH expression
3. Increased number of granulosa cells
4. Acquisition of LH receptors by expressing the LH receptor gene
   The dominant follicle will survive the drop in FSH by expressing more FSH receptors & acquiring LH receptors so that it can bind to the small amounts of LH & FSH present

Question 15

Describe the process of steroidogenesis in ovaries?

Answer 15

acetate -> cholesterol -> pregnenolone -> progesterone -> androgens -> oestrogen

• P450 side chain cleavage enzyme converts cholesterol -> pregnenolone which is a precursor for progesterone
• 17 alpha hydroxylase converts progesterone into androgens
• Aromatase converts androgens into oestrogen

Question 16

What triggers the LH surge?

Answer 16

• Early follicular phase = negative feedback: High E2 = low FSH
• Late follicular phase = positive feedback: High E2 (>300pmol) = LH surge
• The steady increase in E2 makes the pituitary more responsive to pulses of GnRH from the hypothalamus, so the switch to positive feedback results in an LH surge

Question 17

What happens as a result of the LH surge?

Answer 17

1. Resumes Meiosis I - forms secondary oocyte arrested in Meiosis II
2. Ovulation - secondary oocyte released into fallopian tube

Question 18

***Describe the cascade of events in ovulation

Answer 18

1. Blood supply increases to the follicle
2. Appearance of apex or stigma in ovary wall
3. Enzymatic breakdown of ovary wall by proteases & inflammatory mediators
4. 12-48 hrs after peak of LH, follicle wall is digested & ovulation occurs releasing cumulus-oocyte complex
5. Secondary oocyte collected by fimbria & moves down fallopian tube by peristalsis & action of cilia

Question 19

Describe the effect of the LH surge on the meiotic division of primary oocyte?

Answer 19

• LH surge triggers the resumption of Meiosis I. Initially arrested in Prophase I of Meiois I
• Completes first meiotic division, where primary oocyte forms a secondary oocyte & first polar body
• Half of the chromosomes are put in the first polar body & it plays no further part in the process
• Secondary oocyte begins Meiosis II but arrests again. It has the majority of the cytoplasm

Question 20

What triggers the second meiotic division of the secondary oocyte?

Answer 20

• The secondary oocyte spends 2-3 days in the fallopian tube
• These secondary oocytes are arrested in Metaphase I of Meiosis II
• Fertilisation triggers the resumption of Meiosis II

Question 21

Describe the formation of the corpus luteum

Answer 21

• Once ovulation has occured, in the early luteal phase remainder of follicle forms corpus luteum
• Corpus luteum has both luteined theca & granulosa cells
• These lutenised cells lead to an increase in progesterone, oetsrigen is also produced but progesterone dominates
• Granulosa cells produce:
  1. INHIBIN - prevents release of FSH to prevent further growth, also helping to decrease oestrogen levels
  2. P450 scc - cleaves cholesterol into pregnenolone which is the precursor for progesterone
• Corpus luteum continues making progesterone until placenta forms

Question 22

What receptors are present on the corpus luteum & how does this support it?

Answer 22

• Corpus luteum has LH receptors
• The corpus luteum is supported by LH & hCG (human chorionic gonadotrophin). hCG also binds to LH receptors
• In the event of fertilisation, hCG is released by the placenta to prevent degradation of the CL

Question 23

How do hCG levels change after ovulation?

Answer 23

• hCG levels rise exponentially in the first few months of pregnancy but then drop once the placenta is established

Question 24

What are the two secretions of the corpus luteum?

Answer 24

1. Progesterone

2. Oestrogen

Question 25

What are some of the key clinical applications of the control of the menstrual cycle?

Answer 25

• GnRH analogues can be used to shut down the HPG axis so that it can be stimulated externally
• E.g precocious puberty, IVF