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Physio Female Reproductive
Physio Female Reproductive
47
Medical
Graduate
03/20/2010

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Term
Genetic Sex
Definition
-gonads are bipotential till 5 weeks
-in males, testes develop in 5-7 wks
-in females, ovaries develop at 9 wks
-genetic sex normally determines gonadal sex
Term
SRY gene
Definition
-'sex determining region on Y' chromosome
-on non-pairing region of Y chromosome (no crossing over with x)
-normally, its' always retained on Y
Term
What happens if SRY gene translocates to X chromosome?
Definition
-SRY from non pairing region translocates to X chromosome
-get X+sry sperm that fertilized X egg
-so get XX male, with underdeveloped testes
Term
What happens is SRY gene is mutated or deleted?
Definition
-get XY female (called Swyer's)
-ovary can't make eggs, called a 'streak gonad' which docs tend to remove to avoid cancer
-lack of puberty
Term
cells types in testes
Definition
-germ cells=spermatogonia
-sertoli cells produce anti mullerian hormone (AMH)
-leydig cells produce testosterone
Term
cells types in ovaries
Definition
-germ cells=oogonia
-granulosa cells produce estradiol
-theca cells produce progesterone
Term
Gonadal Sex determination of phenotype
Definition
-testes make AMH and testosterone first
-fetal ovaries do not secrete AMH
-without testes, fetus will default to being female
Term
differentiation of male genitalia
Definition
-testosterone stimulates wolffian duct growth of epididymus, vas deferens, seminal vesicles, ejaculatory ducts
-AMH causes atrophy of mullerian ducts
-penis and scrotum differentiate at weeks 9-10 in presence of dihydrotestosterone (DHT)
Term
differentiation of female genitalia
Definition
-in absense of testosterone, wolffian ducts regress
-in absence of AMH, mullerian ducts develop into fallopian tubes, uterus, upper 3rd of vagina
-in presence of estrogen, ext female genitalia develops (clitoris, labia, lower 2/3 of vagina)
Term
5 alpha reductace
Definition
converts testosterone to dihydrotestosterone (DHT), which stimulates growth of penis and scrotum
Term
When is fetus undifferentiated vs fully differentiated as male?
Definition
undiff at 5 weeks
diff as male at 12 weeks
Term
Androgen insensitivity syndrome
Definition
-also called testicular feminization
-XY, but phenotypically female
-non menstruating
-blind ending vagina
-gynecomastia
-has testes, so makes AMH and get no development of uterus or fallopian tubes
-also makes testosterone but likely an 'androgen receptor defect' so don't get wolfian duct development or conversion to DHT, so end up with female external genitalia
Term
congenital adrenal hyperplasia
Definition
-masculinzation of extermal female genitalia at birth
-normal uterus, fallopian tubes, ovaries
-menstruates at puberty
-XX with ovary so no AMH or testosterone
-but have active adrenal that causes masculinization of external genitalia (large clitoris, fused labia)
-caused by reduced negative feedback on hypo pit axis: poor levels of cortisol cause inc levels of ACTH which causes hyperplasia of cholesterol producing cells in adrenal cortex
-enzyme defect (21 hydroxylase deficiency) causes increased androgen production
-also have reduced aldosterone that causes salt wasting/dehydration
Term
examples of genotype/phenotype discrepancies
Definition
-androgen insensitivity syndrome (testicular feminization)
-congenital adrenal hyperplasia
-
Term
normal adrenal function and feedback
Definition
-high levels of cortisol and/or aldosterone secreted from adrenal gland negatively feedback to hypothalamaic pit axis to inhibit ACTH
Term
What causes puberty?
Definition
-GnRH pulses

Before puberty:
minimal to no GnRH release so low levels of FSH, LH, estrogen, testosterone
-minimal to no folliculogenesis, spermatogenesis

After puberty:
-inc in pulse freq and amp of GnRH release
-inc FSH, LH pulses
-inc estrogen and testosterone
-get folliculogenesis and spermatogenesis
Term
levels of FSH and LH across female life span
Definition
-have spurts during development between 1st trimester and 6 mo./1 yr
-then negligible levels in childhood, rise at puberty, then very high in menopause
-in puberty, see relatively constant level of FSH and cycles of LH
Term
male versus female puberty
Definition
FEMALE
-breast bud
-pubic hair
-peak growth spurt
-ovulation after peak height
-menarche
-adult pubic hair and breasts

MALE:
-genital development
-pubic hair
-spermatogenesis then peak height
-genitalia and pubic hair adult
Term
main driver of puberty in boys?
Definition
-activation of hypothalamic pituitary -hypo pit axis increases leydig cell synthesis and secretion of testosterone
-causes spermatogenesis, penile growth, pubic hair, voice lowering
-growth spurt culminating in closure of epiphyses (hand and wrist commonly used to assess growth)
Term
puberty in girls
Definition
GONADARCHE:
-hypo pit axis drives ovarian estradiol synthesis from granulosa cells
-causes breast bud, linear growth spurt, menarche

ADRENARCHE:
-inc production and secretion of adrenal androgens
-may occurs as early as 2-3 years before puberty onset
-causes axillary hair and pubic hair growth
Term
what are tanner stages
Definition
used to assess stage of puberty
Term
primordial germ cells
Definition
-eventually produce gametes
-are precusors to oogonia and spermatogonia
-start in hindgut of embryo and move to gonads where multiply
Term
primary oocyte
Definition
completes meiosis I at ovulation
Term
secondary oocyte completes meiosis at fertilization
Definition
Term
key events in ovarian cycle
Definition
-follicular growth
-ovulation
-ovary secretes estradiol (E2) and inhibin
-luteal function
-corpus luteum secretes progesterone and estradiol
-luteal regression
Term
follicle growth
Definition
-multiplication of granulosa cells
-development of antrum
-growth of oocyte
Term
What are granulosa and theca cells stimulated by?
Definition
granulosa: FSH
theca: LH
Term
cumulus
Definition
granulosa cells that surround oocyte and zona pellucida (non cellular glycoprotein coat)
-note there are cytoplasmic bridges from cumulus to oocyte for transport
Term
How is estradiol production controlled?
Definition
-FSH induces granulosa cells to aromatize androgens prouduced by theca cells...estradiol is product of this (happens with aromatase)
-granulosa cells also make inhibin which decreases FSH
Term
inhibin
Definition
-made by granulosa cells
-FSH stimulates the secretion of inhibin from the granulosa cells of the ovarian follicles in the ovaries. In turn, inhibin suppresses FSH.
-inhibits FSH production and GnRH release from the hypothalamus
-diminished by GnRH
-stimulated by IGF-1
Term
How is dominant follicle selected?
Definition
it has most FSH receptors
-insufficient FSH causes atresia
Term
describe levels of FSH and LH during follicular phase
Definition
are low, suppressed by neg feedback of estradiol (causes proliferation of endometrium) on ant pit
-during follicular phase, FSH and LH receptors are upregulated in both theca and granulosa cells
Term
How does estradiol cause preovulatory LH surge?
Definition
-usually estradiol causes neg feedback
-but when E2 levels are maintained high for long enough, causes positive feedback to ant pit... becomes more sensitive to GnRH, causing LH surge
Term
How does LH surge affect follicle?
Definition
-oocyte:auses completion of meiosis I, extrusion of polar body. oocyte arrested in meiosis II
-microvilli across zona pellucida are withdrawn
-loosening of cumulus cells
-at ovulation, there is enzyme/prostaglandin induction in follicle wall
Term
transformation of ruptured follicle to corpus luteum
Definition
-theca cells and blood vessels invade
-granulosa cells hypertrophy and terminally differentiate (luteinization)
-ruptured follicle becomes solid corpus luteum
-steroid secretion changes: now secretes progesterone and estradiol
Term
effects of progesterone
Definition
-enhances proteolytic enzymes
-digest and rupture follicle wall
Term
What happens to cervical mucous during ovulation
Definition
increases in quantity and becomes less viscous so sperm can penetrate
Term
decidualization
Definition
terminal differentation of stromal cells in uterus, in order to prep for pregnancy
Term
What is optimal time for implantation?
Definition
-around day 21
Term
What is corups luteum formed from?
Definition
from luteinized granulosa and theca cells of dominant follicle
Term
Why does basal body temp increase in luteal phase?
Definition
progesterone affects hypothalamic thermoregulatory center
Term
blood loss during menses
Definition
-only about 60 ml
-can lead to signifcant loss of iron/anemia
Term
summary of FSH actions
Definition
-stimulate follicle development
-induces aromatase activity in granulosa cells to make estradiol from androgens
-induces formation of LH receptors
-selection of dominant follicle
Term
summary of LH actions
Definition
-produce androgens in theca cells
-stimulates last stages of follicular development
-induces ovulation
-stimulates formation of corpus luteum
Term
where does fertilization take place
Definition
ampulla of fallopian tube
Term
implantation
Definition
-blastocyst hatches from zona pellucida
-appostion to receptive endometrium (decidualization)
-invasion of trophoblast
-corpus luteum maintained by hCG from syncytium
-if no implantation, CL degenerates
Term
placenta
Definition
-placenta makes all pregnancy hormones
-needs cholesterol from mother and fetal adrenal gland to convert progesterone (pregnenolone) to DHEA-Sulfate. placenta needs 17 alpha hydroxylase from fetal adrenal.
-pregnenolone (shunted to adrenal gland where converted to DHEA-S to 16 OH DHEAS in fetus this is shunted back to placenta where it's converted to estriol
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