Female Repro phys Lopez Flashcards
primordial follicle
primary oocyte surrounded by squaous epithelium, beofre pubertry, inactive follicle
early primary follicle
single layer cuboidal follicular epithelium
ZP begins to form
no steroid hormones being made
late primary follicle
several layers of cuboidal follicular epithelial cells
ZP forms glycoprotein coat around oocyte
2ndary follicle
stratum granulosum (stroma around follicle) theca interna and externa (made from stroma) -start to make small amount of androstenodione (interna) still preantral
2ndary follicle antral formation
antrum begins to form
fluid filled space (liquour folliculi)
rich in hyaluronic acid
mature follicle
antrum occupies much of space
oocyte displaced to one side
corona radiata or cumulus oophorus
theca cells have ___ receptors and make what
LH receptors and make androstenodiione from cholesterol, andro sent to granulosa cells
granulosa cells have ___ receptors and receive __ from theca cells and convert it to what via what enzyme
FSH and LH receptors, androstenadione and convert it to estradiol via aromatase
what effect does estradiol made in granulosa cells have
increases FSH sensitivity in granulosa cells which leads to more estradiol syn
-also inhibits FSH and LH, but sensitiation leads to more estrogen overall
The ovary is divided into 2 parts and what is significant about each
outer cortex where ovarian follicle resides within stroma
-highly mitogenic, >80% of ovarian cancer
inner medulla: neurovascular elements run into the medulla
how does the gorwing follicles restrain development of too many primordial follicles
by release of AMH
follicular cells in primary follicle stimulate oocyte growth how
follicle cells stimulate oocyte growth by releasing kit ligand which binds c-KIT on oocyte
when is the follicle known as a primary follicle
when cuboidal granulosa cells first appear
when is follicle known as 2ndary follicle
primary oocyte is surrounded by several layers of cuboidal granulosa cells
-once has 3-6 layers of granulosa cells, secretes paracrine factors to induce nearby stomral cells to become thecal cells
when is the follicle a mature preantral stage
once thecal layer forms
what are signs of the progression of 2ndary follicles
- movement of follicle from outer cortex to inner cortex closer to vasculature of ovarian medula
- follicles release angiogenic factors
in preantral follicles oocyte fails to ____ and begins what
- fails to complete meiosis I bc of lack of specific meiosis-associated proteins
- oocyte begins to grow and produce ZP1,2,3
endocrine function of growing preantral follicle: granulosa cells express ___ but are dependent on __
FSH receptors, dependent on factors from oocyte to grow
-no ovarian hormones at this stage
what is the major product of leydig cells and which enzyme to they have little amt of in growing preantral stage
androstenedione is major product, minimal at this point
-low levels of 17B HSD
growing antral follicles
mature preantral follicles develop into early antral follicles
-once granulosa epithelium increases to 6-7 layers, fluid filled spaces appear btwn cells and form antrum
during growing antral follicles phase swelling of the antral cavity divides granulosa into 2 pops
1) mural granulosa cells (stratum granulosum)
2) cumulus cells (cumulus oophorus or CR)
mural granulosa cells
form outer wall of follicle, close to outerlying thecal layers
- become highly steroidogenic
- remain in ovary after ovulation–>corpus luteum
cumulus cells
- inner cells surrounding oocyte
- during ovulation released from ovary with oocyte so fimbriae can gran and move oocyte along length of oviduct to site of fertilization
meiotic arrest of oocyte is achieved by what
elevated cAMP levels
thecal cells of large antral follicles produce what
-significant amounts of androstenedione and testosterone (much lesser extent)
FSH stimulates what in granulosa cells
- proliferation of granulosa cells
- induces expression of aromatase
- expression of inhibin
- expression of LH receptors in second half of follicular phase
mural grangulosa cells convert androgens to what and also produce increased amount of ____ during early follicular phase
androgens to estradiol 17B
-increase inhibin
low levels of ___ and increased amount of ___ exert a negative feedback on FSH secretion which selects the follicle with the most FSH-responsive cells
estrogen, increased inhibin
primary oocytes begin meiosis I during ___ and complete meiosis I just prior to then become __
fetal life
ovulation
secondary oocyte
secondary oocyte is arrested in
metaphase II until fertiliztion, if this does not occur within 1 day, secondary oocyte degenerates
Thecal cells: basal LH levels stimulate production of steroidogenic enzymes: (3)
and also ___ receptors in thecal cells
3B-HSD, CYP17 (17a hydroxylase), and CYP11A1 (desmolase) and LDL receptors in thecal cells
aromatase converts androstenedione to ___ and
testosterone to ___
estrone
estradiol 17B
significance of LH receptors on granulosa cells
- now granulosa cells are responsive to both FSH and LH which allows high levels of aromatase even with decreased FSH levels
- acquisition of LH receptors also ensures that mural granulosa cells will respond to LH surge
what enzyme converts androstenedione to testosterone
17B -HSD
what enzyme converts estrone to estradiol 17B
17B-HSD
the remaining ___ and ___ become the corpus luteum
thecal cells and mural granulosa cells
structural changes associated with LH surge, release of oocyte
- before ovulation bulge
- LH surge causes release of what =
- __ cells detach from __ and oocyte freed
before ovulation follicle presses against wall of ovary to form bulge called stigma
- LH surge induces release of inflammatory cytokines and hydrolytic enzymes from theca and granulosa cells = breakdown of follicle wall = antral cavity continuous with peritoneal cavity
- cumulus cells detach from granulosa cells and oocyte freed
once cumulus cells and oocyte release from granulosa cells the oocyte releases what
TGF-B and GDF9
- GDF9 stimulates cumulus cels to secrete HA
- cause expansion of oocyte complex so can be captured by oviduct and sperm can locate (sperm have hyaluronidase)
LH surge and basal lamina of mural granulosa cells
it is enzymatically degraded and blood vessels poush into granulosa cells
- granulosa cells also produce angiogenic factors to increase blood supply to new corpus luteum
- VEGF, angiopoietin-2, bFGF
during periovulatory period, LH surge induces shifts in steroidogenic activity of mural granulosa cells by
inhibits aromatase expression, less estrogen, less positive feedback on LH secretion
- vasculariztion of granulosa cells to maker cholesterol available for steroid syn and increase LDL/HDL receptors
- increases expression of proteins and enzymes to produce progesterone
what enzyme converts pregnenolone to progesterone
3B-HSD
corpus luteum formation
-granulosa cells —> ____
after ovulation, antral cavity fills with blood
-granulosa cells become granulosa lutein cells which enlarge and fil with cholesterol esters (fill in antral cavity)
what rescues the corpus luteum from degradation after 14 days
HCG during pregnancy
luteal hormonal output is dependent on basal LH levels
progest output correlated with pulsatile pattern of LH relase
-both FSH and LH reduce to basal levels during luteal phase by neg feedback from progest and estrogen
granulosa lutein cells secrete ____ which further suppresses ___ secretion
inhibin A, suppresses FSH secretion
during follicular atresia which cells persist
thecal cells persist and repopulate the cellular stroma of the ovary
- retain LH receptors and ability to produce androgens
- referred to as the interstitial gland of the ovary
menarche
beginning of menstrual cycles
thelarche
breast development
adrenarche
increase in adrenal androgen secretion
pathway of GnRH and FSH and LH release
Gq receptor
- PLC leads to increase in intracellular calcium which activates calcium channels leading to sustained calcium inside cell
- increased calcium triggers exocytosis of gonadropin too
- PLC leads to DAG to PKC to gene txn
inhibins are produced by ___ cells of the follicle and ___ specifically stimulates the cells to produce them
-what else causes production of inhibin
- granulosa cells and FSH
- LH receptors acquired on gran cells just before ovulation bind LH and this stimulates inhbin production
activins are produced in ___ but ___ FSH release from pituitary cells
produced in same tissues as inhibins, stimulate FSH release from pituitary cells
progestins are only effective at negative feedback of hypothalamus and pituitary gland at __ concentrations
high
high levels of estradiol and progesterone during late follicular phase produce what
postive feedback response and thus facilitate LH surge
besides inhibiting AP the inhibins have ____ effect of _____
intraovarian effect of decreasing androgen production, which can have secondary effects on intrafollicular estrogen production
activins stimulate 2 things
FSH release
stimulate syntehesis of estrogens
where are estrogens in female humans derived
from ovary
adrenal gland
peripheral conversion in adipose tissue
ovarian cells can synthesize their own __ de novo
cholesterol
what can liver convert estradil and estrone into
weak estrogen estriol
the higher levels of estrogen during follicular phase ___ basal body temp
lower
higher levels of progesterone from CL after ovulation __ basal body temp
raise
which cells proliferate during the prolif phase of endometrial cycle
basal stromal cells in the zona basalis
estrogen induces synthesis of ___ receptors in endometrial tissue
progestin
progesterone inhibits ___ prolif but promotes proliferation of ____ ___
-progest stimulates what enzymes
epithelial cell proliferation
promotes prolif of endometrial stroma
17B-HSD and sulfotransferase
-convert estradiol to weaker compounds
early secretory phase of menstrual chycle
characterized by development of network of interdigitating tubes within the nucleolus of endometrial epithelial cells
-stimulated by progest
middle to late secretory phase
vasculariztion of endometrium increases glycogen content increases thickness increases glands become engorged with secretions progest promotes diff of stromal cells into predecidual cells which form decidua of pregnancy
estrogen and progestin combo contraception
decrease GnRH and FSH and LH
- no follicular growth
- no ovulation
progestin only OCP
- causes cervical mucus to thicken and become sticky and insufficient
- inhibit sperm penetration into uterus
- impair motility of the uterus and oviducts
- produce changes in endometrium not conducive for implantation of embryo
- don’t inhibit ovulation
menorrhagia
loss of > 80 mL of blood
dysmenorrhea
painful periods
oligomenorrhea
few, irregular periods
amenorrhea
absence of periods
__ and ___ are often due to dysfunction or cessation of HPO axis
oligomenorrhea and amenorrhea
what is endometriosis and most commonly involves what
tissue that normally grows inside uterus grows outside it
-ovaries, bowel, and tissue lining the pelvis
menopause
due to reduction in estrogen and low levels of inhibin no neg feedback of LH and FSH so levels high
polycystic ovarian syndrome
hyperandrogenism, anovulation, and plycysti covary
-abnormal steroidogenesis and folliculogenesis by androgen excess and anovulation
enlarged polycistic ovaries are known to be associated with increased ____
elevated ___ low ___ and elevated __
DHEA
-elevated LH
-low FSH
elevated testosterone
