Female Repro Phys Flashcards
What is the cortex of the ovary made of? Histology?
Densely cellular stroma
Ovarian follicles reside within stroma
Follicles contain primary oocyte surrounded by follicle cells
Covered by simple epithelium
What are the stages of ovarian follicle?
Resting primordial follicle
Growing preantral (primary and secondary) follicle
Growing antral (tertiary) follicle
Dominant (preovulatory, graafian) follicle
Dominant follicle within periovulatory period
Corpus luteum
Atretic follicles (degenerate before maturity)
Describe primordial follicle
Primary oocyte with surrounding single layer of pregranulosa cells
Describe primary oocyte
Arrested in diplotene stage of prophase I
What is the endocrine function of the primordial follicle?
No ovarian steroid hormone
Release paracrine factors
Follicles stimulate oocyte growth by release of kit ligand (stem cell factor)
Kit ligand binds to c-KIT receptor
Describe primary follicle
Has larger primary oocyte than in primordial follicle
Has cuboidal granulosa cells
Describe secondary follicle
Primary oocyte
Multilayered cuboidal granulosa cells
Thecal cells outside of basement layer (stromal cells differenitated after paracrine signals from granulosa cells)
Formation of capillaries
Movement from outer cortex to inner cortex
Describe gamete in preantral follicles (primary & secondary follicles)
Oocyte does not complete meiosis I
Grows and produces and secretes proteins
Initiates secretion of extracellular matrix glycoproteins (ZP1, ZP2, ZP3) that form zona pellucida
Describe endocrine function of granulosa cells in primary/secondary follicles
Express FSH receptor but are dependent on oocyte factors to grow
Do not produce ovarian hormones yet
Describe endocrine function of thecal cells during primary/secondary follicle
Androstenedione production is absent or minimal at this stage
Describe antral follicles (Graafian)
Granulosa epithelium increases layers
Fluid-filled antrum appears
Granulosa cells divide into mural granulosa cells (stratum granulosum) and cumulus cells (cumulus oophorus or corona radiata)
Dependent on FSH
Describe mural granulosa cells (stratum granulosum)
Form outer wall of follicle
Close to outerlying thecal layers
Become highly steroidogenic
Remain in ovary after ovulation to differentiate into corpus luteum
Describe cumulus cells (cumulus oophorus or corona radiata)
Inner cells surrounding oocyte Innermost layer (relative to oocyte) maintains gap and adhesion junctions with oocyte During ovulation, cumulus cells are released from ovary with oocyte Crucial for ability of fimbriated end of oviduct to grab and move oocyte along length of oviduct to site of fertillization
Describe gamete in antral (Graafian) follicle
Oocyte gains meiotic competence but still maintains meiotic arrest until LH surge
Elevated cAMP maintains arrest
Describe endocrine function of thecal cells in antral (Graafian) cells
Produce significant amounts of androstenedione and testosterone (less extent)
Describe endocrine function of mural granulosa cells
Proliferation stimulated by FSH
FSH also induces expression of CYP19-aromatase
Granulosa cells secrete inhibin
Describe the effects of low levels of estrogen and inhibin on FSH secretion
Exert negative feedback
Contributes to selection of follicle with most FSH-responsive cells
Describe dominant follicle
Out of 20 recruited large antral follicles, largest follicle with most FSH receptors
Becomes preovulatory follicle
Describe gamete of dominant follicle
Oocyte grows at slower late
Arrested in meiosis I
Stalk of cumulus cells attaching them to granulosa cells becomes thin
Describe endocrine function of thecal cells in dominant follicle
Express LH receptors and produce androgens
LH stimulate production of steroidogenic enzymes (3betaHSD, CYP17, CYP11A1), LDL receptors
Androstenedione and testosterone released and diffused to mural granulosa cells or vasculature
Describe endocrine function mural granulosa cells in dominant follicle
High number of FSH receptors
FSH upregulates aromatase gene expression and activity (aromatase converts androstenedione to estrone and testosterone to estradiol-17beta)
Express isoforms of 17betaHSD which drives steroidogenesis toward production of estradiol-17beta
FSH also induces expression inhibin B
FSH also induces expression of LH receptors, so cells still have high levels of CYP19 (aromatase) in face of declining FSH levels
Respond to LH surge
Describe luteinization
Culminates in formation of a corpus luteum, which is capable of producing large amounts of progesterone, along with estrogen, within a few days after ovulation
Describe major structural changes associated with LH surge
Induces release of inflammatory cytokines and hydrolytic enzymes from theca and granulosa cells. These breakdown follicle wall, tunica albuginea, and surface epithelium near stigma (bulge that forms when follicle presses against wall of ovary)
Cumulus cells detach from granulosa cells, and oocyte is freed within antral cavity
Basal lamina of granulosa cells is enzymatically degraded, so blood vessels and theca cells can push into granulosa cells
Describe the indirect effect of LH surge
LH-dependent paracrine factors
Oocyte releases transforming growth factor beta (TGFbeta)-related factor and other extracellular matrix components
Components cause expansion of oocyte complex, making it easier for capture by oviduct and easier for sperm to locate
What do granulosa cells release to increase blood supply to new corpus luteum?
Vascular endothelial growth (VEGF), angiopoietin-2, and basic fibroblast growth factor (bFGF)
Describe gamete after LH surge
LH surge induces primary oocyte release from arrest and completion of meiosis I with extrusion of first polar body
Secondary oocyte then progresses to metaphase II and arrested again until fertilization
Describe LH surge on endocrine function of mural granulosa cells
Shifts steroidogenic activity
Surge transiently inhibits aromatase expression and consequently estrogen production
Rapid decline in estrogen helps turn off positive feedback on LH secretion
Causes vascularization of granulosa cells to make cholesterol available for synthesis and increase expression of LDL/HDL receptors
Increases enzymes to produce progesterone
What is in the medulla of the ovary?
Neurovascular elements
Describe corpus hemorrhagicum
After ovulation, antral cavity fills with blood from ruptured vessles
Describe the granulosa cells of corpus luteum
Become granulosa lutein cells, which enlarge and fill with cholesterol esters.
Cells collapse and fill antral cavity
What does human chorionic gonadotropin do to corpus luteum?
Rescues corpus luteum so that it will maintain during pregnancy
Describe gamete of corpus luteum
If ovulation occurs normally, then corpus luteum is devoid of gamete
Describe endocrine function of corpus luteum
Produces progesterone and increases production from LH surge and peaks during midluteal phase
Estrogen production transiently decreases in response to LH surge but rebounds and peaks at midluteal phase
Progesterone and estrogen levels decline during 2nd half of luteal phase unless increased hCG compensates for decreased LH sensitivity
FSH and LH decreased due to negative feedback from progesterone and estrogen
Describe endocrine function of granulsa luetin cells in corpus luteum
Secrete inhibin A which further suppresses FSH secretion
Describe follicular atresia
Demise of ovarian follicle
Predominant process in ovary
Can occur any time during development
During atresia, granulosa cells and oocytes undergo apoptosis
Thecal cells persist and repopulate cellular stroma of ovary
Thecal cells retain LH receptors and ability to produce androgens (collectively called interstitial gland of ovary)
What is menarche?
Beginning of menstrual cycles
What is thelarche?
Breast development
What is adrenarch?
Increase in adrenal androgen secretion
Describe follicular phase
Phase in ovarian cycle that begins with onset of menses and ends on day of LH surge
FSH stimulates a follicle to complete its development
Granulosa cells of follicles increase production of estradiol, which stimulates endometrium to undergo rapid and continuous growth and maturation
Coincides with proliferative phase of endometrial cycle
Rapid rise in estradiol eventually triggers LH surge, which causes ovulation
Describe luteal phase
Phase in ovarian cycle that begins day of LH surge and ends at onset of next menses
Follicle transforms into corpus luteum
Luteal cells produce progesterone and estrogen, which further stimulate endometrial growth and development
Coincides with secretory phase of endometrial cycle
Describe the hypothalamic-pituitary-ovarian axis
Neurons in hypothalamus synthesize, store, and release GnRH
GnRH binds to receptors on gonadotrophs, resulting in synthesis and release of FSH and LH
FSH and LH stimulate ovary to synthesize and secrete sex steroids estrogen and progestins
Ovaries also produce peptides inhibins and activins
Steroids and peptides exert negative/positive feedback on hypothalamus and anterior pituitary
Describe LH release in response to GnRH in early vs late follicular phase
Early: Burst of GnRH elicits only a small rise in LH
Late: Burst of GnRH triggers large release of LH
High levels of estradiol enhances sensitivity to GnRH in late phase
What stimulates inhibin production?
Produced in granulosa cells
FSH stimulates production
Estradiol also stimulates production
Before ovulation, LH can stimulate production
Describe negative feedback by inhibins
Inhibits FSH secretion by gonadotrophs of anterior pituitary
Also have intraovarian effect of decreasing androgen production, which can have secondary effects on intrafollicular estrogen production
Describe positive feedback by activins
Stimulates FSH release (independent of GnRH action)
Also have intraovarian action of stimulating synthesis of estrogens
Describe positive and negative feedback of estrogens and progestins on HP axis
Positive feedback with activin to induce LH surge at end of proliferative phase
As luteal phase begins, negative feedback with inhibin to decrease FSH and LH
What is the major follicular product during follicular phase?
Estradiol
What are the major products from corpus luteum during luteal phase?
Progestins and estradiol
Describe hormonal regulation of basal body temperature during monthly cycle
Higher levels of estrogen present during pre-ovulatory (follicular) phase lower BBT
Higher levels of progesterone released by corpus luteum after ovulation raise BBT
If pregnancy doe not occur, disintegration of corpus luteum causes a drop in BBT that coincides with onset of next menstruation
Describe menstrual phase of endometrial cycle
If oocyte is not fertilized, a sudden diminution in estrogen and progesterone secretion will signal demise of corpus luteum
As hormonal support of endometrium is withdrawn, endometrium degenerates, tissue breaks down, and menstrual bleeding ensues
Day 1 of menstrual cycle
Describe proliferative phase of endometrial cycle
After menstruation, endometrium is restored by 5th day of cycle
Proliferation of basal stromal cells in zona basalis and of epithelial cells from other parts of uterus
Stroma gives rise to connective tissue components of endometrium, and thickness of endometrium increases
Stimulated by estrogen from developing follicles
Estrogen levels rise early in follicular phase and peak before ovulation
Progesterone opposes estrogen action on endometrium epithelial cells but promotes proliferation of endometrial stroma
Progesterone stimulates 17beta-HSD and sulfotransferase
Describe early secretory phase of menstrual cycle
Development of network of interdigitating tubes within nucleolus of endometrial epithelial cells (nucleoloar channel system)
Stimulated by progesterone
Describe middle to late secretory phase of endometrial cycle
Increase in vascularization of endometrium, glycogen content, and endometrium thickness
Endometrial glands become engorged with secrtions
Progesterone promotes differentiation of stromal cells to pedecidual cells, which will form decidua of pregnancy or orchestrate menstruation in absence of pregnancy
Describe effects of contraceptive steroids
Feeds back on hypothalamus (decrease GnRH) and anterior pituitary
Suppressed FSH and LH levels
Low FSH insufficient to stimulate normal folliculogenesis
Low LH means no LH surge, so inhibition of ovulation
Describe progestin effect of oral contraceptive pill
Causes cervical mucus to thicken and become sticky/insufficient
Inhibits sperm penetration into uterus
Impair motility of uterus and oviducts, so decrease transport of ova and sperm to distal uterine tube
Decreased glandular production of glycogen and thus diminished energy for blastocyst to survive in uterus
Progestin-only does not inhibit ovulation like combination pills
Describe endometriosis
Most commonly affects women of reproductive age
Common cause of female sterility
Painful disorder in which tissue that normally grows in uterus grows outside it
Areas bleed each month and result in inflammation and scarring
Clinical presentation: chronic pelvic pain, dysmenorrhea, dyspareunia (painful sex), rectal pain and constipation, infertility
Describe polycystic ovarian syndrome
Most common cause of infertility in women
Manifest during adolescence
Ovarian dysfunction: abnormal ovarian steroidogenesis and folliculogenesis
Enlarged polycistic ovaries with increased androgen levels (DHEA)
High androgens promote atresia in developing follicles and disrupt feedback relationships
Presentation: young, obese, hirsute females of reproductive age, oligomenorrhea or secondary amenorrhea, infertility
Eleveated LH, low FSH, elevated testosterone
Describe Turner syndrome
If half of cases, complete absence of second X chromosome
Interna/external genitalia typically female
Germ cells do not develop, and gonad consists of connective tissue-filled stalk
Clinical: short stature, characteristic webbed neck, low-set ears, shield-shaped chest, short 4th metacarpals, and sexual infantilism
Describe menopause
Occurring 12 months after last menstrual period
End of menstrual cycles
Due to reduction in estrogen, low levels of inhibin, so no negative feedback of LH and FSH
High LH and FSH
