Menstrual Cycle Flashcards
What is the purpose of menstruation?
- Selection of a single oocyte
- Regular spontaneous ovulation
- Correct number of chromosomes in eggs (i.e haploid)
- Cyclical changes to the vagina, cervix and fallopian tube
- Preparation of the uterus
- Support of the fertillised dividing egg
How is the menstrual cycle controlled?
- By secretion of GnRH in a pulsatile manner
- Stimulates the anterior pituitary to produce FSH and LH which occurs in a pulsatile fashion
- Stimulates release of oestrogen and progesterone from theca and granulosa cells
- Theca cells will contain LH receptors which allow for the production of androgens (especially androstenedione made from cholsterol ) and progesterone
- Granulosa cells will contain FSH and LH receptors
- Granulosa cells convert androstenedione into estradiol through activation via the aromatase enzyme by FSH
- LH receptors is only acquired in the follicle selected to become the dominant follicle
What happens when LH is administered in a continous way?
Secretion will drop and switch off completely
Pulsatile secretion is crucial for proper secretion of gonadotrophins
How many phases of the menstrual cycle are there?
2
When does the menstrual cycle begin?
On day 1 - the first day of bleeding
What are the two phases?
- Follicular phase - follows on from 1st day of bleeding growth of follicle and selection of follicle
- OVULATION - occurs at the end of follicular phase, middle of the cycle (empty follicle becomes the corpus luteum)
- Luteal phase - stage dominated by the corpus luteum,
What hormones mainly control the follicular and luteal phase?
Follicular phase - growth of follicles up to ovulation = dominated oestradiol production from dominant follicle
Luteal phase - formation of corpus luteum from the empty follicle dominated by progesterone production from CL
How do we work out the cycle of a woman clinically?
Ask from the 1st day of bleeding to the 1st day of bleeding in the next cycle
What type of feedback controls the luteal phase?
Negative feedback of progesterone
What type of feedback controls the follicular phase?
Follicular phase=variable
- Release of negative feedback
- Negative feedback then reinstated, then
- Switch from negative to positive feedback
Summarise the menstrual cycle
- At the end of the cycle the corpus luteum which was left over after ovulation starts to break down and progesterone LEVELS FALL
- This high progesterone was exterting negative feedback at the level of the hypothalamus + pituitary keeping FSH/LH
- As the levels fall FSH increases and stimulates follicles to grow and produce oestradiol (E2)
- Oestradiol (E2) feedsback to the hyp-pituitary to inhibit FSH release + levels again
- High sustained levels of oestradiol over 300pmol for 48 hours cause the switch of oestrogen to posotive resulting in a massive surge of LH = ovulation of the dominant follicle
- Ovulation of the follicle will result in the remainder of the follicle to become the corpus luteum and progesterone exerts negative feedback to switch off LH and FSH
7.
Why is the inter-cycle rise in FSH important?
Allows selection of a single follicle that will go on to become the dominant follicle that will ovulate
What is the peak of FSH below the LH peak a result of?
As a result of an ‘artefact’ of gonadotrophin stimulation of pituitary by oestrodiol
What is the window of opportunity for the follicle?
- Exact moment when FSH goes up and selects a follicle and then FSH declines and other follicles die
What happens to the selected follicle?
Doubles in size every 24 hours and makes lots of E2 which will exert negative feedback on the hypothalamic pituitary axis to decrease FSH levels
What is the FSH threshold hypothesis?
- One follicle from the group of antral follicles in the ovary at the right stage at the right time becomes the dominant follicle
- This goes on to ovulate
- This is called SELECTION
What happens during dominant follicle selection?
- 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 a fall in FSH?
- Increased sensitivity to FSH
- Increased FSH receptors
- Increased by numbers of granulosa cells
- Acquisition of LH receptors
Describe the formation of androgens and what stage this occurs?
Androgens are formed when the granulosa cells acquire LH receptors producing androgens
What do both theca and granulosa cells contain?
- Cholesterol
- Pregnenolone
- Progesterone
What do only theca cells have?
Androgens
What do only granulosa cells have?
Oestrogens
Where do steroids originate from?
Cholesterol from the removal of sequential C atoms by a series of enzymes
Describe the LH surge
- During the follicular phase, E2 feedback is negative
- At the end of the follicular phase, when the E2 levels are raised for long and high enough the feedback switches from negative to posotive
- Causes a release of LH from pituitary + exponential rise in LH in serum
- Triggers ovulation cascade and egg release
- Corpus Luteum is formed
- Corpus luteum has both luteinised granulosa and theca cells
- E2 production falls, but still produced and P is stimulated & dominates
Describe the events of ovulation
- Blood flow increases to follicle
- Appearance of apex or stigma on ovary wall
- Local release of proteases and inflammatory mediators
- Enzymatic breakdown of protein of the ovary wall
What is released at the beginning of ovulation?
- 12-18 hours after peak of LH
- Follicle wall becomes digested
- Ovulation and release of cumulus-oocyte complex
How long does the process of the LH surge and ovulation take?
15 minutes
What happens to the oocyte after the LH surge?
The nucleus of the oocyte in the dominant follicle completes the first meiotic division
What are the polar bodies which are formed?
- In response to the LH surge the nucleus of the oocyte in the dominant follicle completes the first meiotic division
- You get unequal division of the cytoplasm and a small polar body is extruded - the majority of the cytoplasm is retained within the oocyte as the oocyte will have to carry the early fertilised embryo as all the sperm can bring is its DNA
What meiotic divisions occur at what stages?
- Oogonia to primary oocyte - primary oocyte is arrested in meiosis 1
- LH surge - nucleus of the oocyte in dominant follicle completes the first meiotic division
- Fertilisation - Second meiotic division is completed
How long is the oocyte in the uterine tube?
2-3 days
What happens to the follicle after ovulation?
- Corpus luteum is formed ‘yellow body’
- Progesterone production increases greatly, also E2
What supports the corpus luteum?
- CL contains a large number of LH receptors
- CL supported by LH and hCG (from implanting embryo, if a pregnancy occurs) which will also bind to LHr
What are the hormonal changes during a pregnancy?
- End of ovulation there is a large surge in hCG and gradual increase in oestrogen
- The corpus luteum is maintained and releases progesterone
Why does the CL secrete progesterone?
- Supports oocyte in its journey
- Maintains the CL
- Prepares the endometrium
- Controls cells in the fallopian tubes
- Alters secretions of the cervix
Why does the CL secrete oestradiol?
For the endometrium
How does CL demise occur?
- If fertilisation doesnt occur, CL has a finite lifespan of 14 days
- Removal of CL essential to initiate new cycle
- Cel death occurs, vasculature breakdown, CL shrinks
How can the disruption of negative feedback affect the cycle?
Can cause infertillity and needs to be treated by clomid
What can be used to replace hormones?
HRT = hormone replacement therapy
What can be used to induce a constant negative feedback?
Oral Contraceptive Pill
What can be used to induce gonadotrophin release?
Analogues of GnRH
What can be used to treat infertillity?
Injections of LH and FSH
What are the signs of ovulation?
- Tender breasts
- Abdominal bloating
- Light spotting
- Changes in cervical mucus
- Slight pain or ache on one side of the abdomen
How do ovulation prediction kits work?
E3G is a urinary metabolite of oestradiol allowing women to identify days of high fertility leading up to ovulation
What is the lifespan of an egg?
Up to 24h after ovulation
What is sperm surivival dependant on?
The type and quantity of mucus within the cervix and quality of sperm
