Menstrual cycle and ovulation Flashcards
During fetal development what phase are follicles arrested in?
Meiosis I Prophase, until the LH surge
When does the seocnd meiotic arrest occur?
Metaphase II due to elevated MAPK proteins
- Only resumes meiosis II when/if fertilization occurs
What are the three stages of the ovarian follicle cycle?
- Follicular phae
- Ovulatory phase
- Luteal phase
Describe the follicular phase
- Ovarian follicle: the fxnl unit of the ovary it performs gametogeic and endocrine fxns
- Premenopausal cycling ovary contains follicular structures at different stages
Describe the primordial follicle.
- Primary oocyte arrested in the first meiotic phase, surrounded by a single layer of pergranulosa cells
- It releases paracrine factors and NO steroid hormones
- Represents the ovarian reserve, most of these will undergo atresia
Describe a primary follicle.
- Central primary oocyte found in the center with a single layer of granulosa cuboidal cells
- Incerease in size of the folicle occurs due to the growth of the primary oocyte
- Early production of glycoproteins ZP1,2,3,4
Describe a secondary follicle.
- Primary oocyte surrounded by 3-6 layers of cuboidal granulosa cells
- Secretion of paracrine factors occurs inducing local stroma cells to differentiate into the thecal ccells
- inner thecal cells are glandular and highly vascular
- Fibrous apsule like theca externa
What occurs around the follicle as it progresses to a secondary follicle and what does it allow for?
- Increase in vascularization around the follicle
- Follicles release angiogenic factors creating the vasculature wreath around the follicle providing nutrients for follicle
- ZP also develops providing binding sites for sperm
What are the fxns of preantral follicle cells?
Minimal endocrine fxn
- granulosa cells express FSH receptors but are dependent ono paracrine factors from oocyte for growth
- Granulosa cells aren’t producing ovarian hormones yet
- Thecal cells are aalagous to leydig cells expressing LH producing androstenedione
what marks the antral phase in follicular phase of ovarian cycle?
- appearance of antrum
- oocyte becomes suspended in fluid surroundeed by the cumulus oophorus
What oes an increase in follicular size depend on?
- Increase in antral size
- Volume of follicular fluid
- Proliferation nof granulosa cells
What are mural granulosa cells?
- Makes up outer wall of the follicle and becomes highly steroidogenic
- aka stratum granulosum
What are cumulus oophorus/radiata cells?
- Mainatain gap and adhesion jxns with oocyte
- released during ovulation with oocyte
What are thecal cells in the mid antral follicle growth responsive to?
LH,, this causes them to synthesize androgens from acetate and cholesterol
What are granulosa cells in the mid antral follicle growth responsive to?
- FSH
- COnverts the androges from the thecal cells into estrogens with aromatase
- Induces expression of LH receptors in the late follicular phase
When does the oocyte become competent to complete meiosis I?
Antral stage
What allows meiotic arrest to occur?
Maintenance of elevated cAMP
How does sensitivity to FSH aid in selection of follicles?
- During the follicular phase FSH levels begin to decline due to inhibin and estrogen being produced by the mural granulosa cells
- The largest follicle with the most FSH receptors will become the dominant follicle and the rest undergoes atresia
What is the preovulatory period?
- Time from onset of LH surge to ovulation where structural chages occur in preparation for ovulation
- CHanges in the sterroidogenic fxn of theca and mural granulosa cells occurs, preping for luteinization, CL formation, and increasing progesterone production
How does the LH surge impact granulosa cells?
Causes differentiation of granulosa cells into granulosa lutein cells
- thecal and mural granulosa cells will express LH receptors at the surge
- Inhibition of aromatase expression occurs decreasing the positive feedback on LH secretion
- Increases vascularization of granulosa
What structural changes does LH surge induce?
- breakdown follicle wall tunica albuginea and surface epithelium via release of cytokines and hydrolytic enzymes from theca and granulosa
- Cumulus oocyte complex becomes free floating in the antrum
- Basal lamina of mural granulosa cells is degraded and increased blood supply to follicle/ CL occurs
- LH surge induces oocyte to pregress to metaphase II
What is the luteal phase?
- Antral cavity fills with blood and cell debris called corpus hemorrhagicum
- granulosa lutein cells collapse into antral cavity
- filledd with cholesterol esters
- theca blood vessels and WBC fill rest of cavity
Describe the corpus luteum.
- Corpus luteum of menstruation lasts for 14 days if no pregnancy occurs and then becomes the corpus albicans
- IF pregnancy occurs it is saved by hCG and it stays throughout pregnancy
What does CL do for pregnancy?
- Produces increasing aamounts of progesterone transforming uterine lining into adhesive and supportive structue for implantation
What is follicular atresia?
- Apoptosis of ovarian follicle ( granulosa cells and oocytes) that can occur during any time in development
- Thecal cells persist and repopulate the cellular stroma of the ovary
- Thecal cells keep LH receptors and ability to produce androgens, called interstitial gland of ovary
- Thecal cells persist and repopulate the cellular stroma of the ovary
How is GnRh released? Describe it in the early and late follicular phase.
- pulsatile from the hypothalamus
- in early follicular phse gonadotrophs arent sensitive, each burst gives slight rise in LH
- Later in follicular phase gonandotrophs in ant pit become very sensitive to GnRH in portal blood and it triggers a larger relase of LH
Where do inhibins come from and what do they do
- FSH stimulates granulosa cells to produce inhibins before ovulation
- Inhibins will inhibit FSH production in a negative feedback manner
Before ovulation what do LH and FSH act on?
cells of the developing follicle:
- Theca cells-LH
- Granulosa cells LH and FSH
After ovulation what does LH act on?
Corpus luteum cells
where are activins produced and what do they do?
Granulosa cells same as inhibins, but activins will stimulate FSH releases from the pituitary
For most of the menstrual cycle estrogens and progestin exert negative feedback on HPA, but what is unique about the difference in estrogen and progestin in this NFB cycle?
- Estrogens exert negative feeback at low and high concentrations and progestinns are effective only at high cocentrations
Describe positive feedback in he follicular phase.
- Estradiol levels rise gradually during first half of follicular phase and then steeply during second half
- After they reach certain threshold HP axis reverses it sensitivity to estrogens and exerts a PFB
- This promotes the LH surge
During the late luteal phase, what leads to decreases in levels of progesterone, estradiol, and inhibin?
Demise of the corpus luteum
After onset of menstruation what happens with GnRH?
The HP axis returns to follicular phase patteron of LH secretion resulti in a gradual increase in GnRH pulses
High levels of __ during pre ovulatory follicular phae of menstrual cycle lowers BBT.
Estrogen
Higher levels of _____ released by the ___ after ovulation raises BBT. If pregnancy doesn’t occur this structure disintegrates andc causes a drop in BBT coinciding with the next menstruation.
Progesterone and CL
What phase does the follicle synthesize estrogen?
Follicular phase
What phase does the corpus luteum synthesize estrogen?
Luteal phase
In the endometrial cycle what is the menstrual phase?
- If pregnancy didn’t occur, estrogen and progesterone secretions from CL decrease and it regresses
- The endometrium degenerates and tissue breaks down resulting in menstrual bleeding
- Day one of the cycle
Describe the proliferative phase of the endometrial cycle.
- Occurs on day 5
- Proliferation of basal stromal cells in zona basalis and epithelial cells
- Stroma will give rise to CT components of endometrium
- Proliferation and differentiation of endometrium are stimulated by estrogen
- levels of estrogen rise early in the follicular phase and peak before ovulation
Describe the secretory phase of the endometrial cycle.
- Final phase of uerine cycle corresponds to luteal phase of ovarian cycle
- Middle to late phase:
- vascularization endometrium increases along with glycogen content
- Progesterone promotes differentiation of stromal cells into predecidual cells
Describe menopause.
12 months after last menstrual period marks loss of ovarian reserve
- occurs usually around 51 yrs of age
- due to reduction in estrogen and low levels of inhibin
- NO NFB of LH and FSH so high LH and FSH levels
Menopause sx
In months or years leading up to menopause symptoms are:
- irregular periods
- vaginal dryness
- hot flashes
- night sweats
- mood changes
- weight gain slow metabolism
- thinning hair and dry skin
- loss of breast fullness
