The Menstrual Cycle

Question 1

What kind of secretion of GnRH does there have to be?

Answer 1

→ pulsatile

Question 2

What does the antral follicle produce and what does this do?

Answer 2

→ Estrogen
→ Progesterone

→ feedsback to hypothalamus and pituitary

Question 3

What is the first day of the menstrual cycle?

Answer 3

→ The first day that bleeding occurs

Question 4

What is the length of an ideal menstrual cycle?

Answer 4

→ 28 days

Question 5

What is the follicular phase?

Answer 5

→ Growth of follicles until ovulation

Question 6

What is the main hormone in the follicular phase?

Answer 6

→ Estrogen from granulosa cells

Question 7

What happens to the follicle after ovulation?

Answer 7

→ It becomes the corpus luteum from empty follicle

Question 8

What does the corpus luteum produce?

Answer 8

→ Progesterone

Question 9

What kind of feedback does progesterone have in luteal phase?

Answer 9

→ negative

Question 10

Describe the hypothalamic/ovarian axis

Answer 10

1) Progesterone produced from the corpus luteum exerts negative feedback on the hypothalamus
2) If there is no pregnancy the CL dies and progesterone levels drop - no negative feedback

3) FSH levels rise again - intercycle rise in FSH
4) the early antral follicles respond to FSH and grow again
5) the follicles are producing estrogen
6) This exerts a negative feedback and FSH drops
7) the antral follicles start to die except the dominant one
8) the dominant follicle grows exponentially and produces a lot of estrogen
9) Estrogen levels are sustained for 48 hours over 300pmol
10) there is positive feedback which results in a big increase in LH but not FSH because the dominant follicle produces inhibin which inhibits FSH
11) completion of Meiosis I and entry into meiosis II
12) LH produces proteases which ‘cut’ the oocyte out and cause it to be ovulated
13) It also triggers luteinization
14) CL produces progesterone

Question 11

Why is the intercycle rise and fall in FSH important?

Answer 11

→ It allows the selection of a single follicle which will go on to become dominant follicle

Question 12

What is the rise in FSH for?

Answer 12

→ Selection of antral follicles

Question 13

What is the drop in FSH for?

Answer 13

→ The dominant follicle survives and the others die off

Question 14

What type of growth occurs consistently?

Answer 14

→ Pre antral growth

Question 15

What kind of follicles need FSH to grow?

Answer 15

→ follicles that have an antrum

Question 16

What is the FSH threshold hypothesis?

Answer 16

→ One follicle from the group of antral follicles is at the right stage at the right time
→ It has the most number of FSH receptors

→ It becomes the dominant follicle which goes on to ovulate
→selected follicle double in size every 24hrs and makes lots of E2
→reinstating negative feedback at pituitary causing FSH levels to fall prevents further follicle growth

Question 17

Describe how the dominant follicle survives the fall in FSH

Answer 17

→ The gene which produces the LH receptor is switched on
→ Follicle responds to LH
→increases E2 production because of increased aromatase levels

→ increases FSH receptors so it is responsive to falling levels of FSH
→ increases the number of granulosa cells
→Dominant follicle acquires LH receptors on granulosa cells by FSH

Question 18

What receptors do theca cells have?

Answer 18

→ LH receptors

Question 19

What do theca cells produce?

Answer 19

→ androgen

→ progesterons

Question 20

What is the pathway to make estrogen?

Answer 20

Acetate
↓

Cholesterol
↓
Pregneneolone
↓
progesterone
↓
testosterone/androstenedione
↓
Estrogens

Question 21

What are the three things that can affect the hypothalamic axis?

Answer 21

→ Stress
→ hyperinsulinemia

→ Adipocytes

Question 22

Why are estrogen levels raised at the end of the follicular phase?

Answer 22

→ The dominant follicle produces a lot of estrogen

Question 23

What does the raised estrogen level (produced by the dominant follicle) cause?

Answer 23

→ Estrogen feedback switches from - to +
→ Massive release of LH from the pituitary

→ triggers ovulation

Question 24

Describe ovulation

Answer 24

→ Blood flow to the follicle increases
→ Increase in vascular permeability which increases intra-follicular pressure

→ stigma on the ovary wall
→ local release of proteases
→Enzymatic breakdown of protein of the ovary wall

→ A hole appears in the ovary wall and ovulation occurs
→Oocyte with cumulus cells is extruded from the ovary

Question 25

What happens to the egg after ovulation?

Answer 25

→Follicular fluid may pour into Pouch of Douglas sending signals to fimbrae
→ Collected by the fimbria
→ progresses down the tube by peristalsis and action of cilia

Question 26

What is the advantage of remaining in meiosis I ?

Answer 26

→ Permits the oocyte to retain all of the DNA and remain as large as possible

Question 27

What happens to the chromosomes when the egg becomes a secondary oocyte?

Answer 27

→ 1/2 the chromosomes are put in a small package in the egg called the 1st polar body

Question 28

If pregnancy occurs what is the CL supported by?

Answer 28

→ LH

→ HcG(rises exponentially during first stage of pregnancy

Question 29

What are the functions of progesterone?

Answer 29

→ Alters secretions in cervix
→ Prepares endometrium
→controls cells in Fallopian tubes
→supports oocyte in its journey

Question 30

What is the lifespan of the CL and what happens if there is no fertilisation?

Answer 30

→ 14 days
→Cell death occurs, vasculature breakdown, CL shrinks
→removal of CL essential to initiate new cycle

Question 31

How do we know there is nothing wrong with other non-selected follicles?

Answer 31

because if given FSH injections can pick them all up.

Question 32

What is the oestrogen feedback through the follicular phase?

Answer 32

negative

Question 33

What causes the switch from negative to positive feedback at the end of the follicular phase?

Answer 33

→if E2 levels raised for long enough (48h) and high enough (>300pM) enough then feedback switches from negative to positive
→Causes massive release of LH from pituitary

Question 34

What cells are found in the corpus luteum?

Answer 34

→has both luteinised granulosa and theca cells

Question 35

What happens 12-18 hours of LH peak?

Answer 35

→follicle wall is digested and ovulation occurs with release of cumulus-oocyte complex (COC)

Question 36

What are the secretions of the CL?

Answer 36

→progesterone

→ oestradiol- for endometrium

Question 37

What do clinical applications centre around?

Answer 37

→concept of feedback

Question 38

Name some clinical applications

Answer 38

→disruption of
negative feedback -
clomid
→constant negative
feedback - OCP
→Replacement- HRT
→analogues
→pulsatile treatment
→injections
one or both

Question 39

Which phase of the menstrual cycle is variable?

Answer 39

→Follicular phase

→Luteal phase is strictly 14 days

Question 40

What are the signs of ovulation?

Answer 40

→slight rise in basal body temperature, typically 0.5 to 1 degree, measured by a thermometer
→Tender breasts
→Abdominal bloating
→Light spotting
→Changes in cervical mucus
→Slight pain or ache on one side of the abdomen due to size of dominant follicule

Question 41

How long is the fertile period?

Answer 41

→6 days

Question 42

What is the lifespan of the fertile period affected by?

Answer 42

→Lifespan of the egg → up to 24h after ovulation
→Lifespan of sperm → median=1.5days but sperm can survive up to 5 days in the sperm supportive mucus of fertile days of cycle

Question 43

What chemical do ovulation kits measure?

Answer 43

→E3G is urinary metabolite of oestradiol, allowing women to identify days of high fertility leading up to ovulation.
→Increase in E2 which triggers surge in LH