Lecture 32: The Menstrual Cycle and Ovulation Flashcards
Be able to draw the process of oogenesis (up to fertilization of ovum)
Be able to draw the LH, FSH, Inhibin, Estradiol and Progesterone throughout the menstrual cycle on the slides
Ok
What is active in oocytes at these stages?
Arrest at Prophase I
Arrest at Metaphase II
Resumption of Meiosis II after fertilization
- elevated cAMP
- elevated MAPK
- degeneration of MAPK
What are the characteristics of the primordial follicle?
- arrested at prophase I
- single layer of pregranulosa cells
- most will degenerate, only dominant ones reach ovulation
What are the characteristics of the primary follicle?
What proteins are produced?
- primary oocyte
- cuboidal layer of granulosa cells
-produces Z proteins (1 - 4)
What are the characteristics of the secondary follicle?
- 3-6 layers of cuboidal granulosa cells
- preantral, minimal endocrine function
Describe the changes that occur in the oocyte as it develops from pirmary to secondary follicle
- secrete paracrine factors that induce stromal cells to differentiate into thecal cells
- increased vascularization
- zona pellucida develops binding sites for sperm
How does the primary follicle increase vascularization?
- migrate from outer cortex to inner cortex to be closer to ovarian vasculature
- release angiogenic factors to induce the development of arterioles
What is the difference between thecal and granulosa cells at the secondary follicle level?
Thecal: analogous to Leydig > has LH receptors
Granulosa: analogous to Sertoli > has FSH receptors, produces minimal androstenedione
How does the antrum develop in secondary follicles?
-follicular fluid (antrum) grows around egg along with granulosa proliferation > forms the cumulus oophorus/corona radiata
What are the two types of granulosa cells found in the antral phase and how are they different?
Mural granulosa/stratum granulosum: outer wall, steroidogenic
Cumulus granulosa: form gap and adhesion junctions with the oocyte and released with it
What happens to the thecal and granulosa cells during the antral phase?
Thecal: responds to LH - forms androstenedione (from acetate and cholesterol) which diffuses to granulosa
Granulosa: responds to FSH (and LH later) creates aromatase to convert androstenedione to estradiol
Describe the growth of the follicles during the antral phase
- grows rapidly, slows as it gets larger
- have the ability to complete meiosis, but are all arrested at prophase I (elevated cAMP)
How is the dominant follicle selected?
Candidates: large antral follicles
Mural granulosa secretes low estrogen and inhibin B > FSH levels decline > the large antral follicle with the most FSH receptors becomes the dominant follicle > becomes the Graffian follicle
What is the periovulatory period and what happens to the oocyte during this time?
- time from LH surge onset to ovulation (about 32-36 hours)
- structure changes to prepare for ovulation. thecal and mural granulosa will prepare for luteinization (increase production of progesterone and form the corpus luteum)
What are the effects of the LH surge on the thecal cells?
LH receptors increase, makes more androstenedione
What are the effects of the LH surge on granulosa cells?
Strructural: differentiation to granulosa lutein, expression of more LH receptors and increased vascularization
Cellular:
- aromatase inhibition leadingt to androstenedione accumulation that feedbacks to LH
- increased vascularization > increased cholesterol availability for progesterone production
What major structural effects does the LH surge have?
- Theca and granulosa release cytokines and hydrolytic enzymes to break down follicular wall
- cumulus ocyte complex detaches (free floating oocyte)
- basal lamina of mural granulosa degrades > release of angiogenic factors that increase follicle vascularization (corpus hemorrhagicum)
What are the major events of the luteal phase
Antral cavity filled with stuff to form the corpus luteum
- corpus hemorrhagicum forms at the antral cavity, debris removed by macrophages
- granulosa lutein (yellow) cells with cholesterol esters collapse into the antral cavity as well as theca, blood vessels and WBCs
What happens to the corpus luteum after formation?
No fertilization: remains for about 14 days and becomes scar like collagen filled body called corpus albicans
Fertilization: hCG rescues it and stays viable throughout the pregnancy
During pregnancy, what is the role of the corpus luteum?
-hCG > produces more progesterone that prepares the uterine lining for implantation
What happens to the levels of these hormones after the LH surge?
Estrogen
Progesterone
LH
- transient decrease shortly after LH surge, but rebounds and peaks at the luteal phase, decrease as menses phase approaches so there is only 1 ovulation
- increases and peaks at the luteal phase, decrease as menses phase approaches (if pregnant, hCG compensates via the corpus luteum)
- decrease rapidly and suppressed by progesterone and estrogen until menses
What happens during follicular atresia?
- apoptosis of the granulosa cells and occytes of non-dominant follicles
- thecal cells repopulate the ovarian stroma. retain LH receptors and still produce androstenedione
Be able to draw the HP-Ovarian axis along with feedback mechanisms
Ok
What causes the LH surge?
Pulsatile release of GnRH
LH release gets more responsive each pulsatile surge of GnRH > eventually leading to LH surge
What are the differences in FSH and LH stimulation before and after ovulation?
Before ovulation: LH and FSH act on the thecal and granulosa (as in HPO axis)
After ovulation: LH acts on cells of the corpus luteum
What are inhibins and activins?
What stimulates its production?
- Produced by granulosa cells and inhibits/stimulates FSH production by gonadotrophs in the anterior pituitary
- FSH predominantly, but LH just before ovulation as granulosa cells respond to LH
How does positive feedback happen in the HPO axis?
Estradiol levels reach threshold > HP axis switches sensitivity to estrogens > more receptive to estrogen > surge of estradiol
What is the major product of the ovaries during the follicular phase?
Luteal phase?
Estradiol - produced by the follicles
Progesterone (but Estradiol is still substantially produced) - produced by the corpus luteum
How does basal body temperature relate to the menstrual cycle?
Pre ovulatory phase: lots of estrogen = lower BBT
After ovulation: lots of progesterone = higher BBT
Menses: corpus luteum degenerates > no more progesterone = lower BBT
What happens during the menstrual phase of the endometrial cycle?
Egg not fertilized
corpus luteum degenerates > progesterone and estradiol levels fall > endometrial lining degenerates = menses
What happens during the proliferative phase of the endometrial cycle?
Day 5 of menstrual cycle
Follicles secrete estrogen > basal stromal and epithelial cells proliferate > endometrial lining starts to form again + progesterone receptors so endometrium can be maintained by progesterone
What happens during the secretory phase of the endometrial cycle?
Progesterone predominates
Effects:
- increase in vascularization of the endometrial lining
- Increase in glycogen content of the lining
- Increase in secretions of the endometrial glands
- stromal cells differentiate into predecidual cells that form the decidua (mucosal lining that preps uterus for pregnancy or initiate menstruation)
PCOS (polycystic ovarian syndrome)
Main defect
Clinical presentation
- cysts in the ovaries > excess in androgens like DHEA (but low FSH) > leads to atresia of follicles and disruption of the feedback regulation
- young, obese, hirsutism, oligomenorrhea (infrequent menses), infertility
Turner syndrome
Cause
Clinical
- hypogonadism caused by germ cells not developing (gonads filled with lots of connective tissue)
- female external and internal genitalia, FSH is elevated short stature, infertile, webbed neck, lymph and skeletal abnormalities
What is menopause?
- running out of follicles > decreased estrogen and inhibin
- no feedback on LH and FSH so elevated
