The Menstrual Cycle Flashcards
What are the aims of the menstrual cycle?
selection of a single oocyte
correct number of chromosomes in eggs i.e. haploid
regular spontaneous ovulation
cyclical changes in the vagina, cervix and Fallopian tube
preparation of the uterus
support of the fertilised dividing egg
What happens/is the menstrual cycle?
In a 28-day cycle day 1 is typically the 1st day of menses
The first phase of the cycle is the follicular phase = growth of follicles up to ovulation → dominated by oestradiol production from follicles
Midway you get ovulation
The second half of the menstrual cycle is the luteal phase = formation of corpus luteum from the empty follicle → dominated by progesterone production from corpus luteum
What role does the HPO axis play in the luteal and follicular phases of the menstrual cycle?
hypothalamic/ pituitary/ ovarian axis
Luteal phase=Negative feedback coming from progesterone which feeds back onto the hypothalamus and anterior pituitary
Follicular phase=variable feedback
1. Release of negative feedback 2. Negative feedback then reinstated, then 3. Switch from negative to positive feedback
What happens to the hormone levels in the luteal phase?
Lets start at the late luteal phase and early follicular phase
In the luteal phase progesterone is the main dominating hormone which negatively feeds back
As the corpus luteum dies towards the end of the luteal phase, the levels of progesterone drop
What happens to the hormone levels in the follicular phase?
As progesterone levels drop and you move into the start of the follicular phase, that negative feedback is released
That selectively increases FSH, this is known as the inter-cycle rise in FSH
That is responsible for recruiting those antral follicles into the menstrual cycle
As follicles grow they are going to be secreting oestrogen and as oestrogen levels rise they exert negative feedback and FSH levels fall
In the mid cycle, we get a switch to positive feedback
In the mid follicular phase, as the FSH levels fall, the antral follicles will start to die all except for the one follicle which has been selected as the dominant follicle
As that dominant follicle grows it pumps out oestradiol fi you have high oestradiol of over 300picamoles for 2 days, the switch in feedback becomes positive with a big surge in release of LH
That surge in LH causes ovulation in the dominant follicle and conversion of the remainder of the follicle into the corpus luteum
What happens to the corpus luteum at the end of the follicular phase?
That corpus luteum will produce high levels of progesterone which feedback in a negative way to lower LH and FSH production
If no pregnancy has occurred the corpus luteum dies
Why is the inter-cycle rise in FSH important?
The inter-cycle rise and fall in FSH is very important because it allows selection of a single follicle, which will go onto become the dominant follicle that will ovulate
The window of opportunity
As the FSH levels start to rise a cohort of follicles will be recruited into the menstrual cycle and continue their growth
As they continue their growth they will produce oestrogen
This oestrogen will feedback onto the hypothalamus and pituitary and result in a decline in FSH
As FSH levels drop, these now antral follicles will die off apart from the dominant follicle
When FSH levels drop any other follicles can grow any further and die
How does follicle selection happen? What is the FSH threshold hypothesis?
Raised FSH present a “window” of opportunity to recruit antral follicles that are at the right stage to continue growth
FSH threshold hypothesis
- One follicle from the group of antral follicles in ovary is just at the right stage at the right time to survive declining FSH
- This becomes the dominant follicle which goes onto ovulate
- Known as “selection”
- Can be in either ovary
Oestradiol levels rise reinstating negative feedback at pituitary causing FSH levels to fall prevents further follicle growth
As FSH falls, LH increases.
Dominant follicle acquires LH receptors on granulosa cells
Other follicles do not, so they lose their stimulant and die
How does the dominant follicle survive the fall in FSH?
Dominant follicle survives fall in FSH by:
- increases sensitivity to FSH -> increased FSH receptors so able to catch even low levels of FSH
- Increased numbers of granulosa cells:
· 2-5million GC in EFP and 50-100 million at ovulation
· Increases oestradiol (E2) production because of increased aromatase levels
· 200x more E2 in DF than in others
- Acquisition of LH receptors:
· The LHR (LH receptor) gene is switched on by FSH
What is the purpose of the LH surge in the menstrual cycle?
Throughout follicular phase E2 feedback was negative
At end of follicular phase if E2 levels raised for long enough (48h) and high enough (>300pM) enough → feedback switches from negative to positive
Causes massive release of LH from pituitary
Exponential rise in LH in serum
Triggers ovulation cascade
- Egg is released
- Above result in changes in follicle cells = luteinisation i.e. formation of the corpus luteum
- Corpus luteum has both luteinised granulosa and theca cells
- E2 production falls, but still produced and P is stimulated & dominates
What is the cascade of events that results in ovulation?
Ovulation occurs via cascade of events:
- blood flow to the follicle increases dramatically
- appearance of apex or stigma on ovary wall
- Local release of proteases and inflammatory mediators
- Enzymatic breakdown of protein of the ovary wall
12-18 hrs after peak of LH, the follicle wall is digested and ovulation occurs with release of cumulus-oocyte complex (COC)
Oocyte with cumulus cells is extruded from the ovary and picked up by the fallopian tube
Follicular fluid may pour into Pouch of Douglas
egg ‘collected’ by fimbria of Fallopian tube
egg progresses down tube propelled by peristalsis and action of cilia
What is the importance of the completion of the first meiotic division of the dominant follicle?
In response to the LH surge, the nucleus of the oocyte in the dominant follicle completes the first meiotic division.
½ the chromosomes are put into a small “package” in the egg called the 1st polar body
The egg (with most of the cytoplasm) is now a secondary oocyte
The 1st polar body plays no further part in the process and does not divide again
Oocyte begins the 2nd meiotic division, but arrests again.
The egg is ovulated out in this form; with the secondary oocyte and the first polar body and the chromosomes all lined up in the middle
How is the corpus luteum formed?
after ovulation the follicle collapses
corpus luteum is formed, ‘yellow body’ in Latin
progesterone production increases greatly, also E2
CL contains large numbers of LH receptors
CL supported by LH and hCG (from implanting embryo, if a pregnancy occurs) which also bind to LHR
What hormone changes occur at the beginning of pregnancy?
hCG levels will rise exponentially during the first few months of the pregnancy this will coincide with the establishment of the placenta which can then take over the functions from the corpus luteum
What secretions does CL secrete?
secretions of CL: - progesterone: - supports oocyte in its journey - Maintains the CL - prepares the endometrium - controls cells in Fallopian tubes - alters secretions of cervix oestradiol: - For building up the endometrium and keeping it thick
