Female Reproductive System Review (Michels) - MT Flashcards
Describe LH secretion patterns (day and night) during a woman’s:
- Childhood
- Puberty (10-14 years)
- Reproductive years (14-50 years)
- Menopausal stage (50+)
- childhood: scant, little day and night
- Puberty: low during the day, increased/pulsatile during the night
- Reproductive years: Constantly pulsatile day and night
- Menopause: High pulsatile levels day and night
FSH and LH levels in a woman peak during what times between the time of conception of herself as a fetus and her puberty? (2x)
- between the 2nd and 3rd trimesters
- between birth and 6 months
What is occuring on day zero of a woman’s menstrual cycle between the pituitary and ovaries?
- events in pituitary
- events in ovary
- Pituitary responds to falling levels of Estradiol and Progesterone by increasing FSH secretions
- Corpus luteum dies, leading to a decline in Estradiol and Progesterone
What is occuring between day zero and day 13 of a woman’s menstrual cycle between her pituitary and ovaries?
- Pituitary events (2x)
- Ovary events (2x)
*hint: how does the selection of the dominant follicle occur?
- Pituitary
b - Estradiol and inhibin negatively feed back on FSH
d - High Estradiol has positive feedback on gonadotropes –> LH and some FSH surges
- ovaries
a - FSH recruits a cohort of large antral follicles to enter rapid growth phase. Follicles secrete low amounts of E and inhibin.
c - Declining FSH levels cause atresia of all but 1 follicle –> selection of dominant follicle which produces high levels of Estradiol
On day 14 of a woman’s menstrual cycle what is occuring with her pituitary-ovary cross talk?
*hint: ovulation is occuring and corpus luteum has formed at this point
a - LH surge induces metabolic maturation, ovulation and luteinization. Corpus luteum produces high Progesterone and Estradiol + inhibin
The follicular phase occurs when in the average 28 day cycle for a mature fertile woman?
Luteal phase?
follicular 0-14 days
Luteal 14-28 days
are the stages of follicular development?
(x6)
- Primordial follicle
- primary follicle
- secondary preantral follicle
- small antral follicle
- large, recruitable antral follicle
- dominant follicle at ovulation
Primordial follicles grow into primary follicles and then secondary pre antral follicles. This process is identified as the initiation and gonadotropin independent growth phase.
What is occuring to the follicles in this phase regarding:
- follicular growth
- growth regulation
- Is growth dependent or independent of pituitary gland?
1 - Follicles enter early growth
2 - This growth is regulated by paracrine signaling b/t oocyte and follicle cells and b/t growing and resting follicles
3 - growth is Independent from pituitary gland
The secondary preantral follicle stage, small antral follicle and large recruitable antral follicle stage are mediated by the Basal growth phase.
- follicles are dependent on what molecule to grow during this phase?
- what is the follicular sensitivity to growth stimulation during this phase?
- Follicles are dependent on gonadotropins,
- … but have low sensitivity and are not influenced by fluctuations associated with menstrual cycle.
Once follicles reach the stage where they are large and recruitable antral follicles, they are said to enter rapid growth phase. It takes about 14 days for the dominant follicle to be selected at ovulation.
- What are the large recruitable antral follicles sensitive to in this 14 day period of “Hunger Games” like trials?
- How do follicles avoid atresia (being killed, like Rue)?
- Follicles are extremely sensitive to increase in FSH at the end of menstrual cycle and
- extremely dependent on FSH to avoid atresia
Time table for follicular development:
- Time it takes for primordial follicle to become primary and then secondary preantral follicle?
- time it takes secondary preantral follicle to become small antral follicle?
- time it takes small antral follicle to become large recruitable follicle?
- time it takes to select a dominant follicle from the pool of large recruitable antral follicles?
- >3 months
- 25 days
- 45 days
- 14 days
Large recruitable antral follicles contain what two types of cells?
- mural granulose cells
- cumulus cells
Mural granulose cells highly ______ and differentiate into what?
- highly Steroidogenic
- corpus luteum
Cumulus cells are released with ____ upon ovulation and facilitate what vital process?
- OOcyte
- facilitate oocyte capture by oviduct
OOgonium gamete formation into a haploid ovum occurs via meiosis.
- Why are primary oocytes arrested at prophase I?
- what actively keeps primary oocytes arrrested in prophase I?
- Why are secondary oocytes arrested at metaphase II?
- when is the first polar body extruded?
- When does the secondary oocyte complete meiosis and extrude the 2nd polar body??
- levels of proteins required for completion of meiosis are too low, needs adequate levels of CDK1 and Cyclin B to complete meiosis
- High cAMP levels generated by GPR3 produced by oocyte actively maintains arrest
- production of MAPK pathway proteins arrest oocyte at metaphase II
- upon completion of meiosis I
- upon fertilization, this forms the haploid ovum
Folliclar cells include what 2 types of cells?
- Theca cells
- Granulosa cells
- Theca cells respond to what molecule, and as a result produce _______?
- Granulosa cells respond to what molecule, and as a result produce _______?
- *hint: Hypothalamus starts production of these molecules by releasing ______.
- theca cells respond to LH and produce Androgen (androstenedione)
* thecal cells have low levels of 17beta hydroxysteroid dehydrogenase and therefore do not produce large amounts of testosterone
- granulosa cells respond to FSH and produce Estrogen
- GnRH
- In the second half of follicular phase, FSH induces expression of _______ on mural granulosa cells.
- What does this allow to occur?
- FSH induces LH receptor expression on mural granulosa cells
2 allows mural granulosa cells to respond to both LH and FSH and respond to LH surge prior to ovulation.
What type of follicular cells produce inhibins?
granulosa cells
Androgen derived estrogen, estrogen, and inhibins produced by granulosa cells negatively feedback on what hormones?
- LH and FSH production
- At the end of follicular phase what happens to the feedback loop between estrogen, LH, and FSH?
- what event does this trigger?
- The negative feedback of estrogen becomes positive feedback and produces an LH and FSH surge.
- This triggers the LH surge that resulting ovulation
In the luteal phase Theca and granulosa cells promote the production of Estrogen which stimulates an LH surge which stimulates the corpus luteum luteal cells (formed after ovulation) to produce what?
- Lots of progesterone and some estrogen
Luteinization is the process whereby mural granulosa cells experience transient inhibition of CYP19 expression and estrogen production.
What does this do to the positive feedback loop?
turns it off
so that estrogen and progesterone do not simulate LH and FSH release
What is the lifespan of the corpus luteum?
What can prolongs its survival?
- about 14 days
- HCG inflammatory event can rescue it by revascularizating it into the corpus albicans
Estrogen has what effects on the oviducts?(x5)
- Endosalpinx epithelial size
- blood flow
- oviduct specific glycoproteins
- ciliogenesis
- mucus, muscular tone
What does progesterone do to the oviducts? (x3)
- decreases epithelial size
- deciliation of oviducts
- decreases mucus
- relaxes muscular tone
The uterine lumen is made of the endometrium and myometrium. The endometrium is then divided into the functional zone and basal zone.
what happens to the functional zone during menstruation?
It is lost
The uterus is in menstrual and proliferative phases…
- During what days of the cycle?
- During what phase of the ovary?
- 3-5, 10-13
- Follicular
The uterus is in seretory phase during…..
- what days of the menstrual cycle?
- What phase of the ovary?
- 15-18, 22-25
- Luteal
During the Proliferative phase of the uterine wall, the rising levels of estrogen cause what two things to happen?
- causes an increase in cell growth and division of all cell types in the stratum basale
- Also acts to increase expression of progesterone receptors during this time.
During the secretory phase, Progesterone causes what 3 things to occur regarding regulation of the endometrial lining?
- inhibits growth of uterine endothelium by inducing differentiation of epithelial and stromal cells
- Promotes secretion of nutrient rich compounds that supprt blastocyst viability. increase window of receptivity of surface lining
- Opposes actions of estrogen on uterus by downregulating estrogen receptor and promoting conversion of estradiol 17Beta to less potent estrone.
In the menstrual phase, what causes the drop in progesterone levels and onset of menstruation?
Corpus luteum death
Inhibin A is produce by mural granulosa cells in luteal phase. What does it do?
suppresses FSH secretion
Inhibin B are produced by mural granulosa cells.
What does it do?
turns off FSH secretion
The structure and fuction of the cervix.
- property of the lamina propria?
- What is it a gateway to?
- durin luteal phase what does it impede?
- highly elastic lamina propria
- Gateway to elastic lamina propria
- impedes passage of sperm d/t changes in endocervical canal
Estrogen has what effect on the regulation of cervical mucus?
Progesterone?
- Estrogen: stimulates production of a thin, watery slight alkaline mucus
- Progesterone: stimulates production of scan viscous, acidic mucus
Estrogen has what effect on:
- Bone
- Liver
- CV
- CNS
?
- In bone estrogen promotes closure of epiphyseal plates (anabolic and calciotropic hormone)
- In liver, estrogen increases LDL receptor, HDL levels and cortisol binding protein, thyroid hormone binding protein and sex hormone binding protein
- In CV estrogen causes vasodilation through NO synth
- in CNS, estrogen appears to be neuroprotective
Progesterone has what effect on CNS?
regulates set point for thermoregulation
What 2 things transport estrogen?
- 60% bound to sex hormone binding globulin SHBG
- 20% bound to albumin
- 20% free form
What transports progesterone? (x2)
- bound to cortisol bindin protein
- albumin
Where are estrogens metabolized?
- In peripheral tissues, specifically adipose tissue
Key events during fertilization and implantation. (x7)
- 1 days after ovulation
- 4 days after ovulation
- 5 days after ovulation
- 6 days after ovulation
- 8 days after ovulation
- 10 days after ovulation
- Fertilization
- Blastocyst enters uterine cavity
- Implantation
- Trophoblast froms and attaches to endometrium
- Trophoblast begins to secrete HCG
- HCG rescues corpus luteum
Know the chart on slide 23
- Duration of pregnancy is counted from the date of_________?
- Average time of pregnancy?
- date of last menstrual cycle
- 40 weeks total or 38 weeks from ovulation
In the 1st trimester, what rescues the corpus luteum and stimulates luteal production of estrogen and progesterone?
HCG
in the 2nd and 3rd trimesters, the placenta and the fetus take over production of what?
- progesterone and estrogen
What are the limitations of the placenta? (x3)
- cannot make adequate cholesterol
- lacks enzymes for estrone and estradiol
- lacks enzymes for estriol
What does the mother’s body in general (not the placenta) contribute in terms of steroid biosynthesis? What does it lack?
- contributes LDL cholesterol
- lacks adequate synthetic capacity for progesterone and estrogens
What does the maternal placenta contribute in terms of steroid biosynthesis? what does it lack?
- contributes 3beta hydroxysteroid dehydrogenase aromatase (P-450)
- Lacks adequate cholesterol synth capacity
is missing 17alpha hydroxylase, 17 and 20 desmolase, 16 alpha hydroxylase. All for synthesis of estrone and estradiol and estriol
What does the fetus contribute in terms of steroid biosynthesis? what does it lack?
- contributes 17alpha hydroxylse, 17 and 20 desmolase, 16alpha hydroxylase (estrone, estradiol, estriol production)
- lacks 3 beta hydroxysteroid dehydrogenase aromatase provided by placenta
between the mother, placenta, and fetus, which entities are required to produce progesterone?
mother and placenta
- mother for cholesterol
- placenta for conversion of cholesterol into progesterone
What is the biosynthetic pathway which is undertaken between the mother, placenta, and fetus to make estriol?
- What provides cholesterol starting base?
- what converts cholesterol into pregnenolone?
- What happens to pregnenolone in the fetus?
- How does the placenta create estriol? (preproduct and enzyme)
- mother provides cholesterol
- cholesterol converted into pregnenolone in placenta then transported into fetus
3.
- fetus converts pregnenolone into DHEA-sulfate in fetal adrenal glands
- fetus converts DHEA sulfate into 16 OH DHEA sulfate in fetal liver and ships it back over to placenta
4. Placenta converts 16 OH DHEA sulfate into estriol with sulfatase aromatase enzyme
Human placental lactogen (hPL) also known as human horionic somatomammotropin (hCS) is…..
- structurally similar to what two molecules
- detectable in maternal serum at what week?
- After detection, levels increase directly proportional to what factor?
- GH and PRL
- detectable in maternal serum at 3 weeks of gestation
- increases directly proportionally to size of placenta
hPL (HCS) has an antagonistic action to what?
anti insulin effect, diabetogenic
What is the purpose of the diabetogenic effect of hPL? (x2)
- incrases glucose availbility for fetus
- stimulates mammary growth and development (lypolysis)
What can hPL be used as an index of well being for?
Placenta (which makes hPL)
Maternal endocrine changes to the…..
- PItuitary? x2
- Adrenals? x2
- Thyroid? x2
- pituitary:
- 2x increase in size
- ADH set point lowered - Adrenal:
- Cortisol and aldosterone levels rise
- Estrogen stimulates activity of renin angiotensin aldosterone system - Thyroid
- total T3 and T4 increase but free T4 normal
- TSH levels decrease in 1st trimester
Cardiovascular changes during pregnancy include? (increase/decrease)
- Vascular volume?
- peripheral resistance?
- SV
- HR
- Contractility
- CO
- Vascular volume increases
- peripheral resistance decreases
- SV increases
- HR increases
- contractility increases
- CO increases
Respiratory changes during pregnancy? (increase/decrease)
- minute volume
- Tidal volume
- PCO2
- FRC
- IRV
- acid base change?
- minute volume increases
- tidal volume increases
- decrease in PCO2
- decrease in FRC
- decrease in IRV
- Respiratory alkalosis
Renal changes during pregnancy? (increase/decrease)
- ADH, renin, Ang II, aldosterone
- GFR
- ADH, Renin, Ang II, aldosterone increase
- GFR increase
The stages of labor include? (x3)
- Strong uterine contractions
- Delivery of fetus
- Delivery of placenta
Initiation of parturition is caused by? (x5)
- Placental CRH
- Estrogen
- Oxytocin
- Prostaglandins
- Uterine size
After parturition, Prolactin is secreted in a pulatile manner for about 36 weeks.
- This action inhibits what neurons in the hypothalamus?
- The result of this inhibition is?
- Can a woman become pregnant again in this 36 week window?
- Parvicellular neurons
- decreased release of GnRH and thus decreased stimulation of pars distalis gonadotropes leading to decreased LH and FSH secretion and decreased stim of ovaries (lactational amenorrhea in)
- Yes
What does suckling at the nipple stimulate in a woman who has just had a child?
- stimulates magnocellular neurons and parvicellular neurons in the hypothalamus
When stimulated, Magnocellular neurons, through the pars nervosa increases secretions of what?
oxytocin
Oxytocin stimulates what in the breast?
increase in concentration of myoepithelial cells which increases milk let down
When stimulated, parvicellular neurons decrease their secrtion of what?
- Dopamine
decreased dopamine stimulation of pars distalis leads to what?
lactotrophs increase secretion of prolactin
What does prolactin increase do to the breast?
stimulates galactopoiesis which stimulates milk let down
