REPRO: The Menstrual Cycle

Question 1

What are the aims of the menstrual cycle?

Answer 1

• selection of a single oocyte
• regular spontaneous ovulation
• correct number of chromosomes in eggs
• cyclical changes in the vagina, cervix and fallopian tube
• preparation of the uterus
• support of the fertilised dividing egg

Question 2

Menstrual cycle phases?

Answer 2

Follicular Phase- first 14 days (variable)
Ovulation-mid cycle
Luteal Phase-last 14 days (constant)
Menstruation

Question 3

What is the follicular phase of the menstrual cycle?

Which hormone dominates the follicular phase?

Answer 3

First 14 days of the menstrual cycle

• growth of follicles up to follicles
• selection of dominant follicle
• dominated by oestradiol production (oestrogen) from the dominant follicle.
• feedback is variable on the HPO axis

Question 4

What is the luteal phase of the menstrual cycle?

Which hormone dominates the luteal phase?

Answer 4

Last 14 days of the menstrual cycle

• remainder of the empty follicle after ovulation is luteinised and becomes corpus luteum
• ovulation to the end of the cycle.

Progesterone (from corpus luteum)
-exerts negative feedback on the HPO axis

Question 5

Why do GnRH releases have to be pulsatile rather than continuous?

Answer 5

When GnRH release is continuous it leads to a fall in LH release. Whereas when it is pulsatile, LH release remains consistently high.

Question 6

Describe how the feedback in the follicular phase is variable.

Answer 6

1. We get the release of negative feedback
2. Negative feedback is then reinstated
3. Then, we switch from negative feedback to positive feedback

Question 7

first two stages of the menstrual cycle

Answer 7

Late Luteal/Early Follicular

• no fertilisation, corpus luteum dies, no more progesterone production, no more -ve feedback on HPO axis, causing inter-cycle rise in FSH
• increase in FSH stimulates recruitment of antral follicles into menstrual cycle and further growth, producing oestrogen from granulosa cells

Mid-Follicular

• oestrogen exerts negative feedback on HPO axis
• drop in FSH causes antral follicle to die except dominant follicle
• dominant follicle grows in size and contains many granulosa cells which produce tons of oestrogen

Question 8

last 3 stages of the menstrual cycle

Answer 8

Late Follicular
-when oestrogen levels sustained for 2 days (>300pmol), feedback switches to positive

Mid-cycle

• massive LH surge due to positive feedback from oestrogen
• LH surge induces completion of meiosis I and ovulation of cumulus-oocyte complex (day 14)

Mid-luteal

• remainder of follicle is luteinised by LH to become corpus luteum for progesterone production
• progesterone exerts negative feedback, reducing FSH+LH

Question 9

Describe follicle selection.

Answer 9

The raised FSH presents a ‘window’ of opportunity.

The FSH threshold hypothesis:

• one follicle from the group of antral follicles in the ovary is just at the right stage at the right time
• this becomes the dominant follicle which goes on to ovulate
• this is known as ‘selection’
• it can happen in either ovary

Oestradiol levels rise, reinstating negative feedback at the pituitary, causing FSH levels to drop, preventing further follicle growth.

Question 10

What does the LH surge trigger?

Answer 10

completion of meiosis I & ovulation

Question 11

Why is the inter-cycle rise and fall in FSH important?

Answer 11

The intercycle rise and fall of FSH is very important because it allows for the selection of a single follicle.

Question 12

How does the dominant follicle survive a drop in FSH?

Answer 12

As FSH falls, LH increases.

Increases FSH receptors
-to pick up declining levels of FSH (increase sensitivity to FSH)

Increases number of granulosa cells
-more aromatase for oestrogen production

Acquiring LH receptors on granulosa cells
-LH receptor gene is switched on by FSH and causes LH surge

Other follicles do not, so they lose their stimulant and die

Question 13

What are some rules of receptors on follicles?

Answer 13

Theca cells will always have LHr, never FSHr.
- remember that LH drives androgen and progesterone production from theca cells

Granulosa cells will have FSHr, then LHr are required from the mid follicular phase onwards
- FSH and then LH drive oestrogen production in the follicular phase

Question 14

What happens when the dominant follicle is selected?

Answer 14

It grows rapidly, doubling in diameter in seven days, from 7mm to 14mm. It needs masses of growth factors, nutrients and steroids. There is also rapid neoangiogenesis (formation of new blood vessels).
Oestrogen is released from the follicle into the circulation.

Question 15

Describe the LH surge during the menstrual cycle.

Answer 15

Throughout the follicular phase, oestrogen feedback was negative. At the end of the follicular phase, oestrogen levels are raised for long enough that feedback switches from negative to positive.

This causes a massive release of LH from the pituitary. There is an exponential rise of LH in the serum. This triggers the ovulation cascade.

Question 16

What is the ovulation cascade?

Answer 16

Ovulation occurs via a cascade of events:
- blood flow to the follicle increases dramatically (the increase in vasculature permeability increase intra-follicular pressure)

• an appearance of an apex or stigma in the ovary wall
• the local release of proteases
• the enzymatic breakdown of the ovary wall
• 12-18 hours after the peak of LH, a hole appears in the follicle wall and ovulation occurs
• the occyte with cumulus cells is extruded from the ovary under pressure
• follicular fluid may pour into the Pouch of Douglas
• the egg is ‘collected’ by the fimbrae of the fallopian tube
• the egg progresses down the tube by peristalsis and the action of the cilia

Question 17

What collects the egg after ovulation?

Answer 17

fimbrae of the fallopian tube

Question 18

What happens after the egg is collected by fimbriae?

How long does the oocyte spend in the fallopian tube?

Answer 18

progresses down the tube by peristalsis via the action of cilia

About 2-3 days, where if it meets with a sperm, fertilisation will occur.

Question 19

How is the oocyte prepared for division?

Answer 19

The oocyte has been arrested in the first meiotic division.
This permits the oocyte to retain all of the DNA and remain as large as possible during its long wait.

In response to the LH surge, the nucleus of the oocyte in the dominant follicle completes the first meiotic division, but it doesn’t divide!

Question 20

How does the oocyte move from primary to secondary?

Answer 20

Half of the chromosomes are put into an egg called the ‘first polar body’. The egg is now a secondary oocyte. The first polar body plays no further part in the process and does not divide again.

The oocyte begins the second meiotic division, but arrests again.

Question 21

What is the result of meiosis I completion in primary oocyte?

Answer 21

Unequal division of cytoplasm:
-small polar body extruded

-secondary oocyte containing majority of cytoplasm because egg needs mitochondria, proteins etc. to support fertilised embryo through early developmental stages until it attaches to placenta
>secondary oocyte enters meiosis II and arrests

Question 22

Describe corpus luteum formation.

Answer 22

After ovulation, the follicle collapses. The corpus luteum is then formed, often called ‘the yellow body’.

Progesterone production greatly increases, along with oestrogen.

Question 23

Effect of pregnancy on corpus luteum

Effect on corpus luteum if there is no pregnancy

Answer 23

The corpus luteum contains large numbers of LH receptors. The corpus luteum is supported by LH and hCG (from the implanting embryo if a pregnancy occurs) which also binds LH receptors.

no hCG, and corpus luteum dies to initiate new cycle

Question 24

Describe the secretions of the corpus luteum, and what they do.

Answer 24

PROGESTERONE:

• supports oocyte on its journey
• prepares the endometrium
• controls the cells in the fallopian tubes
• alters secretions in the cervix

OESTRADIOL:
- for the endometrium

Question 25

Describe the demise of the corpus luteum.

Answer 25

If fertilisation doesn't occur, the corpus luteum has a finite lifespan of 14 days. The removal of the corpus luteum is essential to initiate the new cycle. Cell death occurs, there is vasculature breakdown and the corpus luteum shrinks. This process is not yet well understood.

Question 26

Signs of Ovulation

Answer 26

slight rase in basal body temperature (0.5-1ºC) tender breasts abdominal bloating light spotting changes in cervical mucus slight pain or ache on one side of the abdomen

Question 27

Ovulation prediction kits test for... What is the lifespan of an egg after ovulation? What is the lifetime of a sperm?

Answer 27

detects the mid-cycle LH surge in the urine up to 24 hours median is 1.5 days but can survive up to 5 days depending on the quality and quantity of cervical mucus