repro Flashcards
Kartagener Syndrome
absence of dynein –> immotile sperm –> infertility for males
TEXT-14
Testis-expressed gene 14: essential for cytoplasmic bridges in mice
sperm - longer in meiosis I or II?
meiosis I takes much longer - which is wh yyou see many more primary spermatocytes
Tunica Albiginea
fibrous capsule of connective tissue around testes. Divides testes into lobules
haploid/diploid for primary/secondary spermatocyte
primary = diploid // secondary = haploid
menstrual cycle length
24-35
GnRH pulsatility for LH
HIGH amplitude, low frequency
how many oocytes do you have?
@ 5 months gestation: 6 million –> 2 million @ birth –> 300k @ puberty –> 0 @ menopause
follicles start to be recruited to mature starting at…
5 months in utero until menopause
follicles become dependent on FSH at the….
secondary follicle stage (defined by formation of the antrum)
hormones at the end of the menstrual cycle
decrease in E and P leads to an increase in FSH, which recruits next round of follicles
actions of FSH on follice
stimulates granulosa cell prolif. stimulates aromatase activity, increases FSH AND LH receptors
3 actions of p on uterus
limit growth, make glands more tortuous, coiling of b.v.
LH surge (3 things)
resume meiosis II and extrude first polar body, ovulation occurs 36 hours after, switches hormone production: E –> E + P
Corpus luteam makes E and P for…
8-10 weeks (Then placenta takes over)
most common contraceptives
OCPs»_space; tubal sterilization»_space; male condom»_space; vasectomy
timing of copper IUD
insert before 7 days after sex, good for 12 years
medroxyprogesterone acete
progesterone only depot injection. Take every 3 months. Ver effect, but people quite because of irregular bleeding
effect of combination pills on androgens
they decrease free T by 1. increasing the binding protein (SHBG), and 2. via (-) feedback –> lower LH and FSH
Patch - contraceptive
like OCP (combined) - similar efficacy. MOA: no ovulation. Replaced weekly
vaginal ring
like OCP: combined, similar efficacy to OCP. change every 3 weeks. MOA: stops ovulation
IUD
P only –> thickens cervical mucosa (woman still ovulates) Works for 5 years.
Implanon
P only. Placed under arm. Works for 3 years. Rapid return to fertility (period within 3 months)
Implanon
progesterone only LARC. Placed under arm - effect for 3 years
Do OCPs increase risk of venous embolisms?
YES, but not to the extent of pregnancy
Do OCP increase CV risk?
only in smokers
How many pregnancies a year?
6 million pregnancies a year, 1/2 are unplanned, of the unplanned, 1/3 will abort
% of women who have had induced abortions
40%
strongest risk factor for abortion-related mortality
gestational age
can use medical abortion..
up to 9 weeks (used in 1/4 of eligible abortions)
mifepristone
blocks the P receptor –> decidual necrosis, increased prostaglandin receptors, cervical ripening
misoprostal
prostaglandin E1 analog –> contractions and cervical ripening. Used with mifepristone, methotrexate, and by itself
side effects of misoprostol
** responsible for most side effects of abortion. GI (nausea, vomiting, diarrhea), and systemic (fever/chills, HA)
methotrexate
blocks cells division. Takes longer (3-45 days), used off label with misoprostal
signs of perimenopause/menopause transition
irregular menses (fewer follicles to make E), and Sx (e.g., hot flashes)
timing of perimenopause
median age is around 45 - 47.5 (MWHS), duration is 4-5 years (can last 2-8 years)
What defines the onset of menopause?
follicular cohort + rate of atresia –> DECREASED ESTROGEN
biochem profile of menopause
decreased estrogen –> increased and LH and FSH
MOA of CVD and OP in post-menopausal women
lower estrogen leads to increased cholesterol & LDL levels, and increased bone lose
smoking and estrogen
smoking increases the metabolism of estrogen –> faster onset of menopause
sstreak gonads seen with
Turner’s syndrome. Need both X’s for normal ovarian function –> accelerated atresia, streak gonads , ovarian failiure
HCG mimcs
LH
endometrial receptivity window
Determined by progesterone. Day 20-24
timing of implantation
at 7 days post-ovulation (blastocyst stage)
when is embryo fully embedded in endometrial stroma?
7 days post-implantation (14 days post-ovulation)
where does embryo implant?
usually mid-posterior of uterus.
functions of syncytiotrophoblasts
- direct contact with maternal blood; 2. secrets hormones (HCG, P4, E2)
most common endocrine disorder in young, reproductive aged women
PCOS
describe the hyperandrogenism in PCOS
chronic, low-grade elevation in androgens coming from ovaries (not adrenal glands, HEAD levels moderately elevated in 10-15% patients)
Dx for PCOS
- hyperandorgenism //2. anovulation or oligo-ovulation (<6-9/yr) // ultrasound - 12 follicles/ovary
anti-Mullerian hormone in PCOS?
it’s elevated = new marker? in PCOS, the granulosa cells are more sensitive to FSH - greater AMH production
long term effects of PCOS
lifetime metabolic disorder, higher risk of endometrial cancer (lack of periods), increase risk of psych disorders
E and P in PCOS
women will have normal E levels, but lower P levels (won’t make P in the 2nd half of cycle) –> chronic relatively unopposed estrogen –> can see thickened endometrial stripe on ultrasound
effect of estrogen on bone
decreases osteoclasts and determines the closure of the epiphyseal plates
estrogen - CV effects
increases blood coagulability (BAD) but improves cholesterol profile: increases HDL, and decreases LDL (Good)
Metabolic effects of estrogen
increases leptin (involved in fat redistribution also), and increases protein synthesis in liver –> including TBG!!!
two roles of P
- prepares uterus for implantation; 2. render uterus refractory to oxytocin until labr
type 3-4 antagonist
mixed agonist/antagonist - binding of receptor to HRE can recruit co-activator or co-repressor
type 2 antagonist
pure antagonist - binding of receptor to HRE recruits co-repressor
Type 1 antagonist
pure antagonist - does not allow the receptor to bind the HRE
exogenous estrogens and cancer risk
INCREASES endometrial and ovarian (E only) and breast (E+P) but DECREASES colon cancer (E+P)
RU486
Progesterone receptor Type 2 antagonist
hormone independent breast cancer
1/3 of cases –> do mastectomy then chemo + rad
hormone dependent breast cancer
2/3 cases - can do adrenalectomy, aromatase inhibitors (part of chemo) or SERM (prophylactic Rx)
SERM
selective estrogen receptor modulators. Are tumoristatic, can be used for prophylaxis Rx after treatment for breast cancer
aromatase inhibitors
used as chemo for ER-positive tumors
Tamoxefin
Type 4 SERM: ANTAGONIST: breast // AGONIST: bone, uterus (bad), maybe CV
Raloxifene
type 3 SERM: ANTAGONIST in breast and uterus, AGONIST in bone and CV
sperm can stay in the cervix for
80 hours.
sperm capacitation
secretions for woman trigger sperm maturation (so it can fertilize egg). characterized by increased motility of sperm
sperm penetrating the cumulus cells
assisted by sperm motility and enzymes (PH20 - hyaluronidase)
What happens in the acrosome reaction?
the sperm adheres to ZP. ZP3 receptor on sperm is activated. Ca entry via T type Ca channels. Activates PLC and IP3. The sustained Ca triggers fusion of outer acrosome membrane with sperm plasma membrane
hallmark of egg activation
Ca oscillations - lead to exocytosis of cortical granules and blocks polyspermy
timing of egg activation
occurs AFTER fertilization. Egg finishes 2nd meiosis –> mitosis –> embryonic dev.
globozoospermia
round headed sperm that don’t have acrosome reaction - can’t move past ZP. Can use ICSI, but success rate is low
PESA and TESE
look at notes
describe fertilization
penetrate cumulus –> penetrate ZP –> merge with egg plasma membrane –> fertilization (2 pro nu) –> egg activation –> block polyspermy
drugs that can cause impotence
beta blockers, exogenous androgens
initiating erection
CNS –> limbic system activates paraS system, which increases cGMP and causes vasodilation. Local reflex supports this
MOA phosphodiesterase 5 inhibitrs
they inhibit phosphodiesterase 5, increase cGMP, MAINTAIN erection (still need the limbic system to initiate erection and get cGMP production)
metabolism of sildenafil
metabolized in liver by CYP3A4 to active metabolite (20% activity). Excreted via kidneys
can’t use PD5 inhibitors with….
nitrates (anti-hypertensives) because both cause vasodilation (dizziness, hypotension, fatal events)
Timing of adrenarche
usually 2 years before secondary sex char (usually thelarche, then pubarche)
timing of thelarche
usually between 8-13
timing of menarche
average age =13 (after gonadarche, takes about 2 years to build up estrogen secretion and increase endometrial lining)
estrogen and height
low levels == bone growth; high levels = close epiphyseal plates
hormone levels in neonates
release from maternal E&P inhibition –> high LH and FSH –> high fetal E and P
sign of puberty
LH pulses at night (represent GnRH pulses because LH has a short half-life)
what initiates pubertal changes?
the hypoT (arcuate nucleus) is released from inhibition –> starts GnRH pulses (This is NOT controlled by the gonads)
signals that inhibit GnRH pulsatility (delay puberty)
GABA (in girls) and Neuropeptide Y (in boys)
Leptin and puberty
leptin promotes puberty (and decreases NPY). It is NECESSARY for gonadarche, but doesn’t prompt the start of GnRH pulsatility
Kisspeptin receptor
GPR54
Kisspeptin
simulates GnRH neurons (in the arcuate nu of the hypoT) -sudden appearance o kisspeptin fibers surround GnRH neuron just before onset of puberty
why is the ureter vulnerable to injury during pelvic surgery? 1
- in a hysterectomy, the uterine artery crosses the ureter ~2” over the ischial spines; 2. the LEFT ureter comes close to the lateral cervix 3. the ureter lies close to the ovarian vessels
what procedure is commonly performed through the rectouterine pouch?
oocyte retreival
what ligaments support the uterus and vagina?
uterosacral and cardinal ligaments
what is the major cause of infertility in females and how to Dx?
tubal obstruction. Dx with hysterosalpingography (radiography)
perineal body
fibromusclar mass anterior to retum. Can tear during labor to enlarge vaginal orfice. Increases chance of vaginal prolapse
when do you start to dev gonads?
6 weeks gestation (from last menses)
prev of mullerian abnormalities in the general pop
4%
most common mullerian abnormality
septated uterus
inhibin
produced by granulosa and Sertoli cells. Decrease pituitary GnRH receptors –> decrease FSH secretion. Increase LH receptors on thecal cells
Klinefelter Syndrome
47XXY. bilateral atrophic testes. Congenital cause of primary hypogonadism
Kallman Syndrome
GnRH precursor doesn’t migrate from nose to hypoT. no LH/FSH (need supplementation), and altered smell
males and infertility
15% couples are infertile. males account for 30% of blame (females - 50%; combined 20%)
5 alpha reductase
turns testosterone into DHT (external virilization and sexual maturation at puberty)
most common location for BPH
around the proximal urethra (transitional zone)
definition of BPH
nodular prostate enlargement due to proliferation of glands, stroma, or both, that LEADS TO lower urinary tract Sx
PCA epidemiology in the US
most common malignancy in men, 2nd most deadly after lung cancer
PCA epidemiology in the word
6th MOST COMMON cancer
high serum PSA levels signal
that the PCA has broken through the basement membrane
The Sx you see with PCA
** most often asymptomatic. Sx = obstructive bladder Sx, pelvic pain, bone pain
origin of PCA
75-80% from peripheral zone / 15-25% from transitional zone. Central zone can be secondarily involved
Chlamydia vs. Gonorrhea
Chlamydia is an IC org –> fewer Sx –> more common than G
Dx for PID
- lower abdominal pain 2. adnexal tenderness, 3. cervical motion tenderness.
ectopic pregnancies are most common in,.
the ampulla
what makes the vagina resistant to micro-org?
Vagina has lactobacilli which make H2O2 –> acidic environment = resistant to many STIs
dysfunctional uterine bleeding
LACK OF OVULATION - means no progesterone & secretory endometrium. Estrogen causes proliferation - outgrows blood supply - breakdown/bleeding
Endometrial atrophy
Lack of estrogen causes endometrium to break down –> common cause of abnormal uterine bleeding in post-M women
three things to know about polyps
they arise from Basalis layer // they are benign (but have different morphology - thick-walled arteries and enlarged glands) // they are focal (sessile or pedunculated)
most frequent tumor in female genital tract
leiomyoma
leiomyoma and hormones
we know hormones have an effect - tumors increase in preg and decrease after menopause. They are sensitive to estrogen (Tamoxifen)
endometriosis
endometrial tissue (glands & stroma) outside of uterus - usually in ovaries or peritoneal cavity
Adenomyosis
endometrial tissue in uterine wall (myometrium)
most common malignant tumor of female genital tract
endometrial carcinoma
Estrogen dependent endometrial carcinoma
during pre-menopause, perimenopause / myometrial invasion is variable, us/minimal, low tumor grade, indolent behavior, genes: PTEN, K-ras
features of endometrial carcinoma, not hyperplasia,
invasion into myometrium, desmoplastic response, cribriform glands, extensive papillary pattern
mutation found in Type 2 endometrial carcinoma
non-estrogen dependent. p53 mutation (can statin for it)
is type 1 or type 2 more common for endometrial carcinoma?
Type 1 = 80-85% // type 2 = 15-20%
in a post-menopausal women with bleeding, consider….
endometrial hyperplasia (most common) or endometrial carcinoma - type 2 (most concerning)
endometroid endometrial carcinoma
type 1 - it was similar to complex atypical hyperplasia. Saw cribriform plates
Serous endometrial carcinoma
type 2 form (can be mixed with clear cell form). Saw complex papillae structure. Can see calcification (psammoma bodies)
staging of endometrial cacner
look at notes
prognosis for ovarian cancer
5 year survival is 30-50%. Staging is the most impt prognostic factor
most common malignant ovarian tumor (overall)
serous carcinoma
genetics seen in serous carcinoma
LOW GRADE: K-ras or BRAF // HIGH GRADE: BRCA1 or BRCA2 –> usually due to +p53
endometroid ovarian carcinoma
genetics: PTEN, K-ras, microsatellite instability (think type 1 endometroid carcinoma). 15-20% accompanied by endometriosis
Origin of germ cell tumors
the oocyte (in the follicle)
malignant transformation of dermoid cyst
can turn into any kind of cancer. Common = squamous cell carcinoma
Dysgerminoma makes up a sig. % of malignant tumors in…
during pregnancy (20-30%), and before age 30 (80%)
prognosis for dysgerminoma
excellent prognosis - 80-90% survival for high-stage disease
cystadenoma
benign form of surface epithelial carcinoma. See a cyst lined by one layer of cells, filled with fluid. Smooth, thin cyst wall.
Call-Exner bodies
seen in adult granulosa - sex-cord stroma tumors. The granulosa tumor cells are trying to form follices!
what kind of ovarian carcinoma can make estrogem?
adult granulosa (sex-cord stroma) –> endometrial hyperplasia and carcinoma (type 1)
4 side effects of PD5 inhibitors
- vasodilation (don’t use with nitrates) 2. CV - hypotension, tachycardis, decreased platelets; 3. GI - heartburn and indigestion 4. eyes - see blue/green
site of 1st lesions - cervical cancer
squamo-columnar junction (transition zone). As you get older, the transition zone moves higher into the cervical canal
high risk HPV strains
16 & 18
Reflex HPV testing
take the residual liquid from the Pap smear, do high risk-HPV testing. (+) = colposcopy , (-) = Pap smear in 1 year
Co-Test
cytology (papsmear) + high risk HPV testing simultaneously. Used in women >30. (-) = come back in 5 years.
cervical cancer subtypes
squamous cell (80%+), adenocarcinoma (glandular - 15%), other (5%)
biggest factor in cervical cancer deaths
never been screened (50% cervical cancer cases)
worst - HPV 16 or 18?
HPV 16 = more carcinogenic (60% all cervical cancers). HPV 18 = 15% - more in adenocarcinomas
how many cases of cervical cancer a year?
15K in the US - 450K in the world
principle age for HPV vaccine
12-Nov
most common cause of abnormal pap dx
ASC-US –> do reflex testing (if women is 25+)
Timing of testing for cervical cancer
START screening at 21. Can do reflex testing at 24. Can to co-test at 30. You don’t want to start earlier because younger women have higher levels of HPV but lower levels of CIN 3
Cases: LSIL on papsmear, no high risk testing
answer: colposcopy (assume the high risk testing could be positive)
Clue: cyclic bleeding
suggest that ovaries/hormones are in tact (even if duration of cycle if abnormal)
19-year old presenting with malignant cancer
think: dysgeminoma
breast changes during puberty
ductal elongation, driven by estrogen. mitotic rate of glandular epithelial cells is greatest in luteal phase (E+P)
what stimulates the differentiation of breast glands
progesterone and prolactin - prepare glands to lactate
what suppresses the lactogenic action of prolactin?
Estrogen and progesterone
supernumerary nipples (polymastia)
secondary to incomplete regression of milk streak
2 etiologies of galactorrhea
- increased prolactin (amenorrhea) 2. increases sensitivity of breasts to prolactin (regular prolactin levels & regular menses)
Sheehan’s syndrome
infarction of pituitary during labor/delivery –> no lactation, etc.
Gynecomastia - causes
due to imbalance between E and androgens. See it transiently in newborns (mother’s E), transiently during puberty (E production before androgens), in elderly - taking drug that decreases androgens
seminal vesicles add…
fructose
alkylation at 17 alpha
makes androgens with more ANAbolic properties - JUICING
Esterification @ 17-beta
makes regular androgens (similar in potency to T and DHT)
what’s a common OTC male hormone supplement?
DHEA
the adrogen potencies
DHEA and androstenedione=weak // testosterone = moderate.// DHT = very potent (but you make very little)
ARA70
it’s a coactivator for AR-testosterone and AR-DHT
which androgen increases prostate size?
DHT
flutamide
its a receptor antagonist. It prevents the binding of the receptor complex to ARA70
Finasteride
blocks 5-alpha reductase TYPE 2 - can decreased BPH and male pattern baldness (both are caused by 5-DHT)
