Reproduction 3: Female Repro/Menstrual Cycle Flashcards
What is the fundamental reproductive unit of the female repro system?
Gonad = ovary, follicle is the primary reproductive unit
What is included in the female reproductive system?
oviducts, uterus, cervix, vagina, external genitalia
What is the internal genitalia derived from
mullerian ducts
GnRH is activated at puberty. What activates it?
Kisspeptin
What promotes secondary sex characteristics?
increased GnRH pulsatility during REM sleep
What stimulates pulsatile release of gonadotropins?
GnRH
What is the differential levels of GnRH at different stages of life?
spikes in fetal and infant development
low during childhood
elevated at night during puberty
elevated spikes during reproductive years
constantly high in menopause due to lack of neg feedback
The menstrual cycle causes physiological changes in what two organs?
ovary and uterus
What are the cycles called for the ovary and uterus respectively?
ovary: ovarian cycle
uterus: endometrial cycle
What causes the monthly menstrual pattern?
HPG axis feedback
Discuss the female HPG Axis
hypothalamus releases GnRH
GnRH stimulates anterior pituitary to release LH and FSH
What does FSH target?
Granulosa cells
What does LH target?
Theca cells and granulosa cells
What do theca cells do?
produce progestins and androgens
What do granulosa cells do?
produce progestins, estrogens, inhibins, and activins
converts androgen precursors to estradiol
What does FSH do?
stimulates follicular development and conversion of androgen precursors to estradiol
What does LH do?
stimulates biosynthesis of estrogens, induces ovulation and luteinization
When is LH higher than FSH?
reproductive years
What do theca cell do and what kind of receptors do they have?
produce androgens and progestin
receptors for LH
What do granulosa cells do and what kind of receptors do they have?
produce estrogens, progestins, inhibins, activins
receptors for LH and FSH
What kind of feedback do estrogens have?
negative and positive!
positive important for ovulation
What are the three phases of the ovarian cycle?
Follicular phase
Ovulatory phase
Luteal phase
What happens in the follicular phase?
Growth of dominant follicle
What happens in the ovulatory phase?
Follicle rupture and release of oocyte
What happens in the luteal phase?
Formation of corpus luteum
What are the three phases of the endometrial (uterine) phase
Menstrual phase
Proliferative phase
Secretory phase
What do HPG hormones do?
drive coordinated physiological changes during the menstrual cycle
What do physiological changes do?
Signal the hypothalamus
When does the proliferative phase occur?
coincident with majority of follicular phase of ovary
When does the secretory phase occur?
coincident with luteal phase of ovary
What occurs during the menstrual phase?
Endometrial shedding
coincident with early follicular phase of ovary
How long is the follicular phase?
variable, 10-14 days
How long is the ovulatory phase?
1-3 days
How long is the luteal phase?
14 days
Describe the stages of a follicle as it passes through the ovarian cycle
primordial follicle -> primary follicle -> secondary follicle -> mature (Graafian) follicle -> (ovulation/follicular rupture) -> corpora lutea -> corpus albicans -> atretic follicle
How do the L and R ovaries coordinate?
Alternate between ovaries every month/cycle. If both go through the cycle at the same time you can get dizygotic twins
When do the number of primordial follicles peak? How many are left at puberty?
Peak at 20 wks gestation. Only 10% left at puberty
What is a follicle?
one oocyte surrounded by a cluster of granulosa cells (germ cell surrounded by endocrine cells)
What does the mature ovary do?
maintain and nurture resident oocyte
mature oocyte and release it at the appropriate time
prepare vagina and fallopian tubes for fertilization
prepare the uterine lining to accept and implant a zygote
maintain hormonal support for the fetus until the endometrium is ready to do so
In the ovarian cycle, what does day 1 signify?
the first day of menses
What is a primordial follicle?
outer layer of pregranulosa cells plus a small oocyte
What stage are oocytes arrested in?
diplotene stage of prophase
What is a primary follicle?
Larger oocyte surrounded by cuboidal granulosa cells
What is required for the follicle to progress from the primordial to primary stage, and where does this happen?
Requires FSH, can happen in utero
What happens in a secondary follicle?
differentiation of stromal cells into theca cells
increased number of granulosa cells that become multilayered
enlargement of oocyte
What happens in a tertiary follicle, and what else is it called?
Early antral follicle
granulosa cells secrete fluid and create antrum
Granulosa cells closest to oocyte secrete
mucopolysaccharides – forms zona pellucida
How long does it take to mature from a primary to a mature graafian follicle?
10-14 days
What is the selection of a dominant follicle based on?
sensitivity to FSH and local paracrine actions of AMH produced by granulosa cells
What iss a graafian follicle?
the dominant follicle
What 3 types do granulosa cells stratify to?
mural cells
cumulus
antral
What do mural cells do?
farthest from oocyte
highest number of LH receptors
most metabolically active
What are the cumulus cells?
near oocyte, shed at ovulation
What are the antral cells?
face antrum, become luteal cells at ovulation
The oocyte is still a primary oocyte, arrested in diplotene stage until what occurs?
the LH surge
What is a graafian follicle characterized by?
enlargement of the antrum presence of cumulus oophorous
What kind of gland is the ovary?
a primary endocrine gland - it has no ducts to convey gametes to the uterus
When is FSH high?
at the end of the ovarian cycle
What does high FSH do?
recruits new cohort of follicles to enter the follicular phase
What do recruited follicles produce, and what does it do?
produce inhibin B, which has a negative feedback on FSH
What is important about low FSH?
only the follicle that is most sensitive to FSH will survive
What happens when there is more LH than FSH?
stimulates steroid generation by theca cells
How does inhibin B influence theca cells?
has a positive paracrine effect to augment steroidogenesis
When does increased GnRH stimulate high levels of FSH and LH release from the anterior pituitary?
mid cycle - ovulation
What activity does estrogen have on the pituitary during the follicular phase?
negative
What feedback does estrogen have on the pituitary during ovulation/
(strong) positive
what feedback does estrogen have on the pituitary during the luteal phase?
negative
what activity does progesterone have during the luteal phase?
inhibits the pulse generator
what do growing follicles produce?
increasing amounts of estrogen
What effect does E2 feedback have on the anterior pituitary during the follicular phase?
favors LH over FSH (high frequency, low amplitude pulses)
What receptors do theca cells have, and what do they produce?
LH –> synthesize androgens
What kind of receptors do granulosa cells have?
LH and FSH
What does FSH do in granulosa cells?
increases number of receptors for LH (responsible for LH surge)
increases aromatase (Cyp19) expression –> converts androgens to E2
What is the two compartment theory of E2 synthesis?
Thecal cells produce androstenedione from cholesterol, which is transported to granulosa cells nd converted to E2
What are the two main events during the ovulatory phase?
LH surge and ovulation
What happens during the LH surge?
switch from negative to positive feedback
Follicle continues to mature
oocyte completes meiosis I and begins meiosis II
Where is the secondary oocyte arrested during the ovulatory phase, and what allows it to progress?
metaphase II - meosis will complete upon fertilization
What happens during ovulation?
expulsion of oocyte-cumulus complex out of ovary
increased inflammatory cytokines
breakdown of ovarian wall
What is the positive feedback during ovulation?
increased E2 leads to increased LH, which leads to more E2, etc.
What does increased E2 do?
E2 increases progesterone receptors
What will cause a decrease in E2 and break the cycle?
rupture of the follicle
what will decrease as a result of lower E2?
LH
What are the three steps of follicle maturation?
cumulus cell expansion: forms corona radiata and cumulus oophorus
detachment of oocyte-cumulus complex - free floating in antrum
follicle forms bulge against ovarian wall (stigma)
what is an oocyte that has completed meiosis I and is arrested in meiosis II?
a secondary oocyte + a polar body
What is ovulation?
rupture of ovarian wall and extrusion of cumulus-oocyte complex
What occurs after extrusion of the cumulus-oocyte complex?
differentiation of mural granulosa cells into large luteal cells and theca cells into small luteal cells
What is the corpus luteum?
remnant follicle
What is the major hormone product during the luteal phase?
progesterone, lesser amounts of E2
during the luteal phase, what does the follicle no longer produce, and what is the effect?
follicle no longer produces inhibin B, and thus less negative feedback on FSH
What inhibin predominates during the luteal phase, and what produces it?
Inhibin A (does not inhibit FSH), produced by the corpus luteum
What are the hormonal effects on the HPG axis during the luteal phase?
high progesterone and E2 decrease GnRH, LH, and FSH
What happens to the corpus luteum in the presence of low LH?
it is degraded
How can the corpus luteum be rescued?
LH equivalent (hCG) produced by the implanted fertilized embryo
What does the absence of HCG and LH cause?
decrease in E2 and progesterone, degradation of endometrium, beginning of menses
What occurs at the end of the ovarian cycle?
death of the corpus luteum and drop in estrogen and progesterone levels
What responds to falling P and E levels, and what does it do in response?
Pituitary responds to falling E and P by increasing FSH secretion
What does an increase in FSH secretion cause?
recruits cohort of large antral follicles to enter a rapid growth phase
What do the large antral follicles secrete?
low amounts of E2 and Inhibin B
what does E2 and Inhibin B do?
negatively feed back on FSH
What does a decline in FSH levels do?
cause atresia of all but 1 follicle
What does the dominant follicle secrete?
high levels of E2
What does high levels of E2 do?
positive feedback on gonadotropes resulting in a LH and (some) FSH surge
What does the LH surge do?
induces meiotic maturation, ovulation, and luteinization
What does the corpus luteum produce?
high progesterone, along with estrogen and inhibin A
What does high progesterone, estrogen and inhibin A do?
negatively feedback on LH and FSH, returning them to basal levels
What happens to the corpus luteum?
slowly becomes less sensitive to basal levels of LH, will die if not exposed to LH-like activity (i.e. hCG)
What are the three layers of the uterus?
endometrium, myometrium, perimetrium
What is the endometrium?
innermost, mucosal layer
What is the myometrium?
thick muscular layer
What is the perimetrium?
(serosal layer) - outer connective tissue and sersa
is the cervix part of the endometrium?
no, it is distinct from the endometrium
What is shed during menstruation?
endometrium - the functional zone
What leads to the necrosis of the endometrial layer?
reduced blood flow to the spiral arteries (high resistance, low volume) leads to ischemia and necrosis of the endometrial layer
What stimulates uterine cell growth
increased E2 during follicular phase
What is dominant in the proliferative phase of the endometrial cycle?
estradiol
What receptors are upregulated in response to E2 during the proliferative phase?
progesterone receptor
What vascular changes occur during the proliferative phase?
increased vascularization
What is dominant in the secretory phase of the endometrial cycle?
Progesterone
What is a result of high progesterone in the secretory phase?
high progesterone from the corpus luteum has anti-estrogenic effects and stops further uterine growth
What do the uterine cells secrete during the secretory phase?
large amounts of carbohydrate rich mucous
What vascular changes occur during the secretory phase?
vascularization continues to increase
What stromal changes occur during the secretory phase?
stromal cells undergo predecidualization and the stroma become edamatous
What is the hormonal state of the menstrual phase of the endometrial cycle?
Low P4 and E2 due to demise of the corpus luteum
What is a result of decreased blood flow to the spiral arteries?
ischemia and necrosis of the endometrium
How else is the endometrium degraded?
proteolytic enzymes are increased
does the released blood clot?
no - the necrotic tissue releases fibrolysins which prevents the blood from clotting
What is the total volume loss in menstruation?
~30 mL
What hormones dominate in the vagina during the mid- to late follicular phase?
estrogens
What is the appearance of the vaginal cells in the follicular phase?
large, squamous, cornified with small or absent nuclei
What hormones dominate in the vagina in the luteal phase
progesterone
What is the appearance of the vaginal cells in the luteal phase?
small basophilic cells with many leukocytes
What are the changes in cervical mucous during the follicular phase?
cervical mucous increases, becomes more alkaline and less viscous
what are the changes in cervical mucous during the ovulatory phase?
characterized by spinbarkeit (stretchable mucous)and ferning (fern pattern when dried on a slide)
What are the actions of estradiol (E2)?
inhibit growth of cohort follicles
alter cervical mucous to facilitate sperm transport
affect fallopian tube to favor transport of ovum and zygote
prepare endometrium for progesterone to evoke secretory response
prime GnRH action on LH secretion o evoke ovulatory surge of LH
What is a primary releaser of E2?
the dominant follicle
