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clinical infertility
The inability to achieve pregnancy after one year of regular, unprotected intercourse or after 6 months if the woman is older than 35
y chromosome contains?
SRY gene which encodes a transcription factor which partially directs the formation of MALE sex organs
Androgens include?
testosterone (T) and DHT
Estrogens include?
estradiol (E2) and estrone
cholesterol
precursor for all steroid hormones
aromatase
converts androgens into estrogens
5-a-reductase
converts test to DHT
DAX1
nuclear receptor protein, transcriptional repressor
SOX9
SRY-related HMG-box genes
XY male hormone cascade
SRY upregulates SOX9 and SF1 which bind to promoter of AMH; inhibits development of female reproductive tract-Mullerian DUcts
XX Female hormone cascade
DAX1-suppresses gene expression of SOX9 and SF1, no AMH; enables development of female reproductive tract-mullerian ducts
internal sexual differentiation time period
begins at 7-10 weeks of a 38 week gestational period
female at sexually indifferent stage
no AMH SRY test, Mullerian ducts develop into uterine tubes and uterus, wolffian ducts degenerate
male at sexually indifferent stage
has AMH SRY TEST, Wolffian ducts develop into epididymis and vas deferens, Mullerian ducts degen
XX male
male despite having two x bc one of x chromosomes contains SRY Gene due to translocation
XY female
morphologically female despite having XY chromosomes bc Y chromosome is missing SRY due to translocation
Male external sex differentiation
Genital tubercle-glans of penis
labioscrotal fold-scrotum
presence of androgen DHT=masculinized external genitalia
each step catalyzed by enzymes encoded by specific genes
female external sex differentiation
Genital tubercle-clitoris
labioscrotal fold-labia majora
absence of androgen DHT=feminized external genitalia
each step catalyzed by enzymes encoded by specific genes
spermatogenesis
begins at puberty
two meiotic divisions of one spermatogonium yield four spermatids-four mature sperm
continuous, gradual decline
time to produce ejaculated sperm?
42-76 days
sperm concentrations
>20million/mL of ejaculate
less than 15 million is infertility
daily sperm production
150 to 275 million spermatozoa
Anterior Pituitary Gonadotropins
LH stimulates Leydig cells
FSH stimulates Sertoli cells
Luteinizing hormone (LH)
leydig cells
produce test during development and inc during puberty
Test essential for spermatogenesis
Follicle Stimulating Hormone (FSH)
stimulates sperm maturation
sertoli cells
regulate sperm development
produce inhibin and androgen-binding protein (ABP)
(test bound to ABP is les lipophilic and cant diffuse out of tubule lumen)
important to keep high concentration of test in lumen for spermatogenesis
test effects before birth
masculinizes the repro tract, precursor for DHT-descent of testes into the scrotum
DHT and test bind the?
Androgen receptor (AR) but DHT has a higher affinity for AR
test effects on sex tissues after birth
Essential for spermatogenesis and oogenesis
• Promotes growth and maturation of the reproductive system at puberty
• Precursor for all estrogens
• Maintains the reproductive tract in adulthood
NES/T
male hormone contraceptive where nesterone suppresses gonadotropins LH/FSH
Condoms
87% effectiveness for preventing pregnancy
Vasectomy
minimally invasive outpatient procedures, sometimes reversible suture back together vas deferens
effectiveness >99%
Spermicide
common chemical used= Nonoxynol-9
creams, gels, included on some barrier methods
degrades acrosome
inhibits sperm motility
Copper IUD
intrauterine device
copper:inhibits sperm motility and acrosomal enzyme activation
All IUDS: in uterine cavity, have strings extend past cervix to check insertion
Oogenesis
1-2 million primary oocytes arrested at meiosis at birth
300k primary oocytes by puberty
400-500 ovulate over lifetime (30-45yrs)
fertilization completes meiosis (secondary ooctyes nucleus fuses with haploid sperm nucleus
Menstrual cycle
last avg 28 days
starts first day of menstruation
ovarian cycle and uterine cycle
Early follicular phase ovarian cycle
days 1-7
formation of estrogens in the follicle depend on thecal and granulosa cells
estrogen negatively feedback on GnRH, FSH, LH
Thecal cells
synthesize androgen
Granulosa cells
convert androgen to estrogen via aromatase
Late follicular phase to ovulation
days 8-14
inhibin causes neg feedback on FSH
right before ovulation, high levels of estrogen and rising levels of progesterone enhance pituitary responsiveness to GnRH= pos feeback of estrogen stimulates LH surge (ovulation occurs 24hrs after LH surge).body temp inc
Early to Mid-Luteal phase (ovarian cycle)
days 15-23
corpus luteum formed from remaining follicular cells after ovulation
Estrogen, progesterone(dominant), and inhibin exert strong neg feedback on GnRH, FSH and LH (prevents ovaries from developing more follicles and releasing oocytes)
Late Luteal Phase (ovarian cycle)
24-28 days
without pregn-corpus luteum degenerates
estrogen and progesterone levels drop triggering menses
Menstrual (uterine cycle)
days 1-5
lack of ovarian hormones, endometrial shedding, menstrual flow
Proliferative (uterine cycle)
estrogen-endometrial building and inc progesterone receptors
days 6-14
Secretory (uterine cycle)
days 15-28
prepares for possible implantation
-inhibits myometrium contractions
-angiogenesis
-nutrient secretion
-cervical plug
phase 1 of Human sexual arousal
excitement-parasympathetic
inc blood flow to genitals
vag lubrication swelling of labia
testes swell scrotum tightens
phase 2 of sexual arousal
plateau-sympathetic
excitement grows
inc in HR, BP, RR and muscle tension
phase 3 of sexual arousal
orgasm-sympathetic
-climactic short phase of sexual response
-sensation of orgasms doesnt differ across sexes
phase 4 of sexual arousal
-body slowly return to unexcited state
-refractory period occurs during male resolution phase (cant become aroused for a period of time)
Erection
parasympathetic response
mediated by NO
Ejaculation (male)
sympathetic response
may/not accompany orgasm
release from storage in vas deferens/epididymis
adult fertility
reproductive years 18-44
fluctuates with menstrual
stays high for sperm-producing individuals
gonadotropin levels LH>FSH
climacterium fertility
age 45-55
menstruation more sporadic
dec/changes in libido
dec in estrogen levels=hormone replacement therpy replaces ovarian sources of estrogen
senescence
age 56+
cessation of menstrual cycle
dec in sperm count
gonadotropin levels highest (FSH>LH)
secondary oocyte only capable of being fertilized for_post ovulation
12-24 hrs
capacitation of sperm
ejaculated sperms are infertile until in the female repro tract for 7-10hrs
site of fertilization
uterine/fallopian tubes
cleavage of zygote
36hr after fertilization
morula=16 cell stage
50-60hrs after fertilization
blastocyst
4 days after fertilization
the inner cell mass forms the embryo then feturs after week 8
the trophoblasts form fetal placenta
implantation in uterine wall
day 8-9 after fertilization
hormone changes during preg
estrogen and progesterone cont inc (corpus luteum during first 8 weeks)
hCG secreted by trophoblast cells as implantation starts(peak at 8wks), allows for persistence of corpus luteum stimulating it to secrete estrogen and progesterone
prevents further menstrual cycles
pre-pubescent
0-7yrs
infertile
gonadotropin levels lowest
FSH>LH
puberty (8-14)
physiologically capable of conceiving
onset of pulsatile GnRH
gonadotropin levels inc and reverse
LH>FSH
Hormonal birth control
progestin, estrogin
pills, shot, IUD
prevents ovulation
birth control pills
either estrogen and progestin or progestin only
taken daily to stop release of oocyte from the follicle (prevent ovulation)
thins uterine lining
thickens cervical mucus
levonorgestrel
class of progestin
binds to progesterone and androgen receptors
slows GnRH release, suppresses LH surge
most effective <24hrs, can take up to 3 days
Ulipristal acetate
requires prescription
binds to progesterone receptor
suppresses LH surge, delays ovulation even if LH surge already occured
most effective <24 hrs can take up to 5 days
birth control shot
contains progestin
stops ovulation, thickens cervical mucus, thins uterine lining
implant birth control
steady dose of progestin
prevents ovulation
thickens cervical mucus
thins uterine lining
hormonal IUD
releases progestin
thicken cervical mucus
thins uterine lining
bilateral tubal ligation
uterine tubes obstructed
not reversible
Bilateral salpingectomy
remove uterine tubes
not reversible