The Menstrual Cycle Flashcards
What are the main 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
How is the menstrual cycle controlled?
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How do we know that GnRH is released in a pulsatile fashion?
- Here they infused an animal with pulsatile GnRH, and the measured LH in the blood. As a reflection of the GnRH. LH is much easier to measure. It follows LH.
- Once GnRH was infused continuously we have a decline in LH secretion.
- Therefore to increase levels of LH we need a pulsatile secretion and in order to switch of the axis infuse continuous levels of GnRH.
In a regular 28 day cycle, what is the first day referred to as?
The first day of menses
What is the follicular phase?
• Follicular phase = growth of follicles up to ovulation → dominated by oestradiol production from follicles
What is the luteal phase?
• Luteal phase = formation of corpus luteum from the empty follicle → dominated by progesterone production from corpus luteum. This stage produces progesterone here.
What happens if no pregnancy occurs?
• If no pregnancy occurs the whole cycle starts again. Ovulation and the MC are cyclical
When does the menstrual cycle begin?
On the first day of bleeding
What are the next 14 days after bleeding
Follicular phase i.e growth of antral follicles
What do the remnants of the follicle form?
Corpus luteam
What phase of the menstrual cycle is after ovulation?
Luteal phase
What occurs at the end if there is no pregnancy?
Menstruation
Describe the feedback of both the follicular and luteal phase
Follicular phase = variable
- Release of negative feedback
- Negative feedback then reinstated, then
- Switch from negative to positive feedback
Luteal phase=Negative feedback → Progesterone (corpus luteam). It acts on the hypothalamus and pituitary to supress the release of GnRH and Gonadotrophins
What happens at the:
- Late luteal phase/ early follicular phase
- Mid follicular phase
- Mid-cycle (ovulation)
- Mid-luteal
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Why is the inter-cycle rise and fall of FSH important?
It allows for the recruitment of the antral follicles into the follicular phase of the ms and the fall allows for the selection of a single follcile from the growing cohort forming the domiant follicle and pre-ovulatory follicle to ovulate
Describe how FSH provides a window of opportunity for a dominant follicle to be selected
- The preantral follicle growth (which is growth of the small follicles which has intiated from the primordial stage) growths through the preantral stage and up to the early antral stage. This is gonadotrophin independent.
- However, once they reach a certain size, to continue growing they need FSH. Once FSH levels rise a cohort of follicles which have been growing will be recruited into the MC to continue growth. They then produce oestrogen which then feeds back onto the hypothalamus and pituitary and results in decline in FSH.
- As FSH level drop these follicles which have been growing die apart from, 1 is selected to become the dominant follicle.
- When FSH levels drop any other follicles which are in the right stage of size, can’t grow further because FSH levels have dropped. This rise and fall of FSH provides a window of opportunity.
How is a dominant follicle selected out of the follicles recruited?
o One follicle from the group of antral follicles in ovary is just at the right stage at the right time to survive declining FSH
o This becomes the dominant follicle which goes onto ovulate
o Known as “selection”
o Can be in either ovary
What prevents further follicle growth once we have selected a dominant follicle?
• Oestradiol levels rise reinstating negative feedback at pituitary causing FSH levels to fall prevents further follicle growth
How does the dominant follicle survive the fall in FSH?
- As FSH falls, LH increases. Dominant follicle acquires LH receptors on granulosa cells
- Other follicles do not, so they loose their stimulant and die
How does the dominant follicle survive the fall in FSH?
Dominant follicle survives fall in FSH by:
o increases sensitivity to FSH = increased FSH receptors – so it can catch low levels of FSH as they are on the dominant follicle.
o increased numbers of granulosa cells – to increase in size:
2-5 million GC in EFP (early follicular phase) and 50-100 million at ovulation
increases E2 production because of increased aromatase levels
200x more E2 in DF than in others
o acquisition of LH receptors
• the LHR (LH receptor) gene is switched on by FSH
Describe the steroid pathway that produces oestrogens
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Describe the feedback of E2 and its affect on LH and ovulaton
• 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
o Egg is released
o Above result in changes in follicle cells = luteinisation i.e. formation of the corpus luteum
o Corpus luteum has both luteinised granulosa and theca cells
o E2 production falls, but still produced and P is stimulated & dominates
What is the cascade of events that causes ovulation?
What happens after 12-18hrs after the peak of LH?
Where does the COC then travel?
o blood flow to the follicle increases dramatically
o appearance of apex or stigma on ovary wall
o Local release of proteases and inflammatory mediators
o Enzymatic breakdown of protein of the ovary wall
12-18 hrs after peak of LH, the follicle wall is digested and ovulation occurs with the 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 by peristalsis and action of cilia
What are the other effects of the LH surge?
- 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.
What happens to the CL after fertilisation?
What is it producing?
What is it supported by?
- corpus luteum is formed, ‘yellow body’
- 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 supporting the CL
When do HCG levels rise?
What does the placenta do in relation to the CL?
- During a pregnancy HCG Levels will rise to very high levels during the first few months and then drop.
- This then establishes the placenta, and take over the functions of the corpus luteam. We no longer need it.
What is secreted from the Corpus Luteum?
progesterone: • supports oocyte in its journey • Maintains the CL • prepares the endometrium • controls cells in Fallopian tubes • alters secretions of cervix
Oestradiol:
• building the endometrium for any implanting embryo.
What happens to the corpus luteum if fertilisation does not occur? (3)
- If fertilisation does not occur, CL has finite lifespan of 14 days.
- removal of CL essential to initiate new cycle
- Cell death occurs, vasculature breakdown, CL shrinks
- Process is not well understood
What are the signs of ovulation?
A slight rise in basal body temperature, typically 0.5 to 1 degree, measured by a thermometer
Need to keep a chart of basal body temp from day 1 of LMP
Why?
• Tender breasts
• Abdominal bloating
• Light spotting
• Changes in cervical mucus – due to steroid hormone levels
• Slight pain or ache on one side of the abdomen
How long is the fertile period and what is it affected by?
- 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 » sperm survival is dependent on the type & quantity of mucus within cervix AND the quality of the sperm
- Quite expensive
What is E3G?
A urinary metabolite of E2 that allows women to identify levels of high fertility leading up to ovulation
Give a summary of the cycle and what are the main points to remember?
- On the X axis we have the days and stages of the menstrual cycle.
- At the start (end of the luteal phase) we have the demise of the corpus luteum.
- This reduces progesterone
- This causes the release of FSH
- This rise in FSH will coincide with the growth of follicles will take off and continue to grow
- As the follicles grow they will produce oestrogen and oestrogen levels rise, it will enter the circulation and act on the pituitary and hypothalamus and result in a fall in FSH.
- This fall in FSH allows selection of a dominant follicle and death of other ones. The dominant follicle will grow exponentially and pump out oestrogen. When levels exceed 300pica moles for 2 days it causes an LH surge. This will peak and surge in mid-cycle. Rise of LH also helps the follicle to survive
- We get the formation of the corpus luteum from the remnants of the egg.
- This then produces progesterone which exerts negative feedback, and LH and FSH to be low.
- If there is no pregnancy the low levels of FSH cause the corpus luteum to die off and progesterone levels fall. All other antral follicles will die due to no FSH.
Main Points To Remember
• Inter-cycle rise in FSH followed by slow decline
• slow rise in LH in follicular phase to exponential mid-cycle rise
• 2 peaks in oestradiol- different shapes ——–
• single luteal phase rise in progesterone ——–
