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Female Reproductive Phys Flashcards

1
Q

HP Axis

A
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2
Q

Female HPO Axis

A

Pulsatile GnRH

Pulsatile LH & FSH

Follicle recruitment & growth

Leads to estrogen production

Increase levels of estrogen leads to endometrial proliferation

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3
Q

Immature HPO

A

estrogen often unable to provide true feedback

Depends on GnRH

Irregular menstrual cycle lenght

Anovulatory cycle

Breakthrough bleeding

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4
Q

Tanner Stages

A

Tanner stage 1= adrenarche

Stage 2= thelarche, breast bud enlarges

Stage 3= peak growth

Stage 4= menarche

stage 5= cyclicity

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5
Q

Adrenarche

A

zona reticularis of adrenal begins to secreate DHEA & DHEAS

6-8 in girls

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6
Q

Thelarche

A

dev of breast prior to menarche

8-1 yo

If breasts develop before 8 yo or do not develop by age 13 signals abnormality

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7
Q

Menarche

A

1st period

8-13 yo

Functional HPO axis

Cycles irregular 6-12 monhts & may be anovulatory

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8
Q

Mature HPO

A

Granulosa cells secrete estradiol E2, inhibin & activin

Estrogens suppress release of GnRH, FSH & LH

Inhibin suppress release of FSH

Activin stimulates FSH release

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9
Q

2 Cell Theory

A

StAR & conversion of cholesterol by CYP 11A are rate limiting!

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10
Q

Different Follicles- Phys version

A
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11
Q

GnRH influence

A

Primary and secondary are GnRH indep

Teritiary/Graafian are GnRH dep

Only those follicles taht respond to FSH/LH will ovulate

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12
Q

Dominant Follicle Selection- extra

A

99.9% of follicles will die

Wave 1= recruitment, growth & largest follicle undergoes atresia

Wave 2= recruitment, growth, selection

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13
Q

Numbers

A

Woman is born with 1 million follicles

Reduced to 300,000 follicles @ menarche

400-500 dom follicles selected for ovulation

Prenatral follicle atresia- Oocytes die first

Basal atresia- reduced androgen production, reduced IGF-3, distrupted theca (reduced vascularization)

Antral atresia- all follicle sizes, more androgens in than in healthy follicles. Granulosa cells first to die, theca are last.

Luteinisation- smaller cells from theca cells & larger from granulosa. Small produce androgen precursors.

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14
Q

2 Cell Follicular Steroidogensis

A

estradiol- pre ovulatory

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15
Q

Estradiol

A

Unbound- 1-2%

Loosely bound to albumin- 60-70%

Tightly bound to SHBG- 25-30% (unavailable)

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16
Q

SHBG

A

Metabolized in Liver

Conjugated & excreted into bile or back into circulation

Excreted in urine if weaker metabolites

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17
Q

Albumin

A
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18
Q

Estradiol R

A

nuclear:

reg transcription

ER a, ERb

well char & widely distributed

mem bound:

rapid non genomic effects

GPR30

F unclear

**estrogen stimulates up reg of ER a B & GPR30 in most tissues

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19
Q

Pre ovulatory HP axis

A

Rise in estrogen causes HP axis

Increase GnRH

Increase LH/FSH

Sustained high levels of estradiol produced by dom follicle

Activin stim FSH secretion

48-96 hr pre ovulation (+ feedback)

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20
Q

HPO Feedback

A

early to mid

  • dominant follicle starts increasing E2
    • feedback reduces GnRH (low lH & Inhibin inhibits FSH)
  • non dominant follicles can’t respond to low FSH & LH
  • vast majority of non dominant follicles undergo atresia

Late follicular

  • dominant follicle produces large amt of estradiol
    • feedback increase GnRH, FSH & LH
  • leads to ovulation
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21
Q

Ovulation

A

High levels of estradiol prime GnRH feedback

High estradiol increase GnRH 48-96 hr

Increase GnRH & stim LH- LH surge

Peak of LH 10-12 hr prior to ovulation

Rapid rise in basal body temp observed during ovulation

22
Q

Ovulation

A

Rupture of follicle

“put a pin through a grape” - that is how much “ruptures”

23
Q

Corpus Luteum

A

Follicle involutes

Follicle remodeled into CL

High VEGF promot blood bessel growth

CL responds to Lh & secretes progesterone

High rate of blood flow needed b/c progesterone NOT stored!

24
Q

Progesterone

A

CL has lifespan of 12-16 days- if not pregnant

Levels of progesterone very low= infertility

If fertilization & implantation= level of preogesterone remain high & escalate during gestation

Progesterone has been shown to inhibit apoptosis of luteal cells

Progesterone essential for CL

25
Luteal Hormone Syn
No FSH required
26
Progesterone Levels
Unbound- 1-2% Albumin bound- 75-80% Bound to Transcortin CBG- 20%
27
Progesterone R
Nuclear: PR, nPR, PGR * reg transcription * PR- A & B * well characterized Mem: * rapid non genomic effects * mPR a, B & g= GPC * PGRMC1= inhibits apoptosis, Essential for ovulatory follicle Progesterone down regulates ERa, B & GPR30 in most tissues.
28
Progesterone Feedback
29
HPO Feedback for luteal phase
Luteal phase * low LH stim progesterone by CL * - feedback by progesterone reduces GnRH & low levels of FSH & LH * follicles cannot respond to low FSH & LH- low FSH inhibit follicle recruitment during luteal phase * LH levels continue to fall during luteal phase due to - progesterone feedback Early- forming CL, rising progesterone Mid- fully dev CL, high progesterone production, hCG rescue Late- if no hCG then progesterone declines & CL apoptosis
30
Summary of HPO
only + feedback is during late follicular phase b/c its right before ovulation.
31
Hyperprolactinemia
32
Menstrual Cycle
Estrogen stimulates during early proliferative phase to heal surface. Progesterone transforms functional layer
33
Menstrual Cycle
Late prolif phase- estradiol peak, ovulation @ end early secretory- CL formed & progesterone rise mid secretory- progesterone levels high, implantation late secretory- decidualization progresses
34
Estrogen & Menstrual Cycle
early prolif * cell division * glandular epith cell cover endometrial surface mid prolif * rapid growth & prolif of functional zone. Max elongation of spiral a. * high VEGF & R * formation of tubular glands * stroma cells prolif rapidly Late prolif * max up reg of estrogen & progesterne R * maintain high level of mitosis * thick functionalis * trilaminar endometirum
35
Estrogen Priming
Prolif phase- estrogens up reg ERs & PRs Secretory phase- window of implantaion, full progesterone action, days 17-24 After 10 days of progesterone action, down reg PR in functional zone & decidualize stromal cells.
36
Decidualization
Morphological & physiological reprogramming of uterine stroma cells under continued influence of progesterone * mid secretory to late- 10 days after progesterone exposure * progesterone stim stromal cell secretion- tightly woven matrix * endometrial epith- DO NOT DECIDUALIZE
37
Decidualization
Receptive endometrium * stroma cells- fibroblast like * expansive ECM * extensive capillary bed Decidualized endometrium * stroma cells contain glycogen droplets * dense ECM- due to stroma cell projections * cAMP dep \*\*\*day 23, stromal cell hypertrophy, increase laminin, fibronectin & collagen. No pregnancy, after day 23 no implantation- cell projections make it easier to shed
38
Progesterone Changes
early secretory * increase progesterone induces glandular sacculation * luminal & glandular epith secreations increase * stromal cells begin to hypertrophy Mid secretory * full progestational effects * max hypertrophy of spiral a. Form dense cap network * large fule stores * window of implantation- functional zone late secretory * stroma cell plump due to glycogen & lipid stores- fuel stores used by blastocyst * decidualization- dense ECM * pre menstraul period
39
Estrogen Summary
prolif- reproductive tissue follicular maturation upreg ER & PR endometrial growth vaginal epith hypertrophy breast dev thinnig of cervical mucus osteoblast prolif - & + feedbcak on hypothal to control FSH & LH & GnRH
40
Progesterone summary
differentiation CL dwonreg ER & pr Sacculation of endometrial glands suppress myometrial contractility hypertrophy of spiral a. thickening of cervical mucus increase basal body temp - feedback on GnRH & suppress FSH & alter LH pulse
41
HPO & Menstrual Cycle
42
Menstruation
Progestrone withdrawal Decrease @ end late secretory phase can also be estrogen or testosterone= just has to be acute reduction /removal of hormone from circulation
43
Menstruation
Vasoconstrict spiral arterioles leads to tissue breakdown leads to ischemia, trigerring tissue degrading enzymes MMPs Tissue & vascular degradation lead to sloughing of functional layer & menstruation
44
Menstrual Blood
25- 80 mL lacks clotting factors 2-7 days
45
Menstrual cycle vs. Menstrual period
menstrual cycle * menses * prolif phase * ovulation * secretory phase menstrual period * only menses portion calculate lenght/ ovulation lenght of period- 14= ovulation!
46
Cuases irregular menstrual cycle
1. hypogonadism- HP dysfunction 2. inherent variability- missed period/ abnorm menses 3. pregnancy 4. pathophys disorders 5. birth control 6. depletion of ovarian follicle reserve
47
Definition
Primary amenorrhea- absence of menarch by age 16 secondary amenorrhea- cessation of menses after menarche has occurred, at least 2 of the prveious 3 cycles or no menses for 6 months oligomenorrhea- infrequent at intervals \> 35 days dysmenorrhea- painful periods polymenorrhea- regular bleeding @ \<21 days menorrhagia- total blood more than 80 mL or longer than 7 days dysfunctional uterine bleeding- excessive non cyclic endometrial bleeding due to anatomy or systemic disease, anovulatory
48
End of Menstrual Cyclicity
woemn over 40= menopause under 40= premature ovarian failure POF depletion of ovarian follicues & cessation of ovarian hormone production
49
Menopause
Very high LH & FSH levels
50
Menopause
Estrone- follicle reserve E1 estrogen of menopause binds to Ers ER lower affinity to E1 than E2
51
Menopause Symptoms
irreg menstrual periods heart pounding/racing hot flashes night sweats vaginal dryness mood swings fatigue headahce decreased libido
52
Pregnancy & Menopausal transition
can still get pregnant because that last follicle can be dominant & get relased BE PROTECTED perimenopause

Physiology (11 decks)

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