Reproductive Flashcards
Sonic hedgehog gene
Produced at base of limbs in zone of polarizing activity
patterning along anteroposterior axis and CNS development
Holoprosencephaly
Wnt-7 gene
Produced at apical ectodermal ridge
Organization along dorsal-ventral axis
FGF gene
Produced at apical ectodermal ridge
Stimulates mesoderm: lengthening of limbs
Homeobox (Hox) genes
Segmental organization of embryo in a craniocaudal direction.
Surface ectoderm becomes
Epidermis; adenohypophysis (from Rathke pouch); lens of eye; epithelial linings of oral cavity, sensory organs of ear, and olfactory epithelium; anal canal below the pectinate line; parotid, sweat, mammary glands
Neural tube becomes
(Ectoderm)
Brain (neurohypophysis, CNS neurons, oligo- dendrocytes, astrocytes, ependymal cells, pineal gland), retina, spinal cord
Neural crest become
(ectoderm)
PNS (dorsal root ganglia, cranial nerves, autonomic ganglia, Schwann cells), melanocytes, chromaf n cells of adrenal medulla, parafollicular (C) cells of thyroid, pia and arachnoid, bones of the skull, odontoblasts, aorticopulmonary septum, endocardial cushions, myenteric (Auerbach) plexus
Mesoderm becomes
Muscle, bone, connective tissue, serous linings of body cavities (eg, peritoneum), spleen (derived from foregut mesentery), cardiovascular structures, lymphatics, blood, wall of gut tube, upper vagina, kidneys, adrenal cortex, dermis, testes, ovaries
Neuroectoderm becomes
Neural plate; Induced by notochord from ectoderm
Nucleus pulposus of the intervertebral disc
Endoderm becomes
Gut tube epithelium (including anal canal above the pectinate line), most of urethra and lower vagina (derived from urogenital sinus), luminal epithelial derivatives (eg, lungs,
liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular cells)
Effect of ACE inhibitors on a fetus
Renal damage
Effect of alkylating agents on a fetus
Absence of digits, multiple anomalies
Effect of diethylstilbestrol on a fetus
Vaginal clear cell adenocarcinoma, congenital Müllerian anomalies
Effect of methimazole on a fetus
Aplasia cutis congenita
Effect of thalidomide on a fetus
Limb defects (phocomelia, micromelia— “fipper” limbs)
Effect of cocaine on a fetus
Low birth weight, preterm birth, IUGR, placental abruption
Effect of smoking on a fetus
Low birth weight, preterm labor, placental problems, IUGR, SIDS
FAS
Pre- and postnatal developmental retardation, microcephaly, facial abnormalities (eg, smooth philtrum, thin vermillion border, small palpebral fissures), limb dislocation, heart defects
Failure of cell migration
Syncytiotrophoblast
Outer layer of chorionic villi; synthesizes and secretes hormones
Umbilical cord
Umbilical arteries (2): return deox blood from fetal internal iliac a to placenta Umbilical vein (1): supplies ox blood from placenta to fetus; drains into IVC via liver or via ductus venosus
What are umbilical arteries and vein derived from?
Allantois
Patent urachus
Total failure of urachus to obliterate → urine discharge from umbilicus
Urachal cyst
Partial failure of urachus to obliterate; fluid- filled cavity lined with uroepithelium, between umbilicus and bladder
Vesicourachal diverticulum
Slight failure of urachus to obliterate → outpouching of bladder
Vitelline duct
connects yolk sac to midgut lumen
Vitelline stula
Vitelline duct fails to close → meconium discharge from umbilicus
Meckel diverticulum
Partial closure of vitelline duct, with patent portion attached to ileum
Melena, hematochezia, abdominal pain
Derivatives of 1st aortic arch
Part of maxillary artery (branch of external carotid)
1st is MAXimal
Derivatives of 2nd aortic arch
Stapedial artery and hyoid artery
Second = Stapedial
Derivatives of 3rd aortic arch
Common Carotid artery and proximal part of internal Carotid artery
(C is 3rd letter)
Derivatives of 4th aortic arch
On left, aortic arch
On right, proximal part of right subclavian artery
Derivatives of 5th aortic arch
Proximal part of pulmonary arteries and (on left only) ductus arteriosus
Pierre Robin sequence
Abnormal development of 1st arch
Micrognathia, glossoptosis, cleft palate, airway obstruction
Treacher Collins syndrome
Abnormal development of 1st arch
Neural crest dysfunction: mandibular hypoplasia, facial abnormalities
Derivatives of 1st brachial pouch
Middle ear cavity, eustachian tube, mastoid air cells
Derivatives of 2nd brachial pouch
Epithelial lining of palatine tonsil
Derivatives of 3rd brachial pouch
Dorsal wings: inferior parathyroids
Ventral wings: thymus
Derivatives of 4th brachial pouch
Dorsal wings: superior parathyroids
Ventral wings: 1. ultimobranchial body
2. parafollicular (C) cells of thyroid
DiGeorge syndrome
Chromosome 22q11 deletion Aberrant development of 3rd and 4th pouches T-cell deficiency (thymic aplasia) and hypocalcemia (no parathyroid development) Cardiac defects (conotruncal anomalies)
Cleft lip
failure of fusion of the maxillary and medial nasal processes (formation of 1° palate)
Cleft palate
Failure of fusion of the two lateral palatine shelves or failure of fusion of lateral palatine shelves with the nasal septum and/or median palatine shelf (formation of 2° palate)
Default embryologic genital development
Female
Mesonephric duct degenerates and paramesonephric duct develops
Development of male genitalia
- SRY gene on Y: testis- determining factor
- Sertoli cells secrete Müllerian inhibitory factor: suppresses development of paramesonephric ducts
- Leydig cells secrete androgens that stimulate development of mesonephric ducts
Paramesonephric (Müllerian) duct development in female
Internal structures: fallopian tubes, uterus, upper portion of vagina (lower portion from urogenital sinus)
Paramesonephric (Müllerian) duct development in males
Appendix testis
Mayer-Rokitansky- Küster-Hauser syndrome
Müllerian agenesis
1° amenorrhea (lack of uterine development) in females with fully developed 2° sexual characteristics (functional ovaries)
Mesonephric (Wolffian) duct in males becomes
Internal structures (except prostate): Seminal vesicles, Epididymis, Ejaculatory duct, Ductus deferens (SEED)
Mesonephric (Wolffian) duct in females becomes
Gartner duct
XY with dysfunction of Sertoli cells or MIF
Develop both male and female internal genitalia and male external genitalia
5α-reductase deficiency
Inability to convert testosterone into DHT: male internal genitalia, ambiguous external genitalia until puberty (↑ testosterone: masculinization)
Bicornuate uterus
Incomplete fusion of Müllerian duct
Uterus didelphys
Complete failure of fusion: double uterus, cervix, vagina
Gubernaculum remnant in males and females
Males: Anchors testes within scrotum
Females: Ovarian ligament + round ligament of uterus
Venous drainage of gonads
Left ovary/testis → left gonadal vein→ left renal vein → IVC
Right ovary/testis → right gonadal vein → IVC
What structures drain to the para-aortic lymph nodes?
ovaries/testes
What structures drain to the external iliac nodes?
Body of uterus/cervix/superior bladder
What structures drain to the internal iliac nodes?
Body of prostate/cervix/corpus cavernosum/proximal
vagina
What structures drain to the superficial inguinal nodes?
Body of distal vagina/ vulva/scrotum/distal anus
What structures drain to the deep inguinal nodes?
Glans penis
Infundibulopelvic ligament
aka suspensory ligament of the ovary
Connects: ovaries to pelvic wall
Contains: ovarian vessels
Ureter courses close behind
Cardinal ligament
Connects: cervix to side wall of pelvis
Contains: uterine vessels
Round ligament of the uterus
Connects: Uterine fundus to labia majora
Derivative of gubernaculum
Travels through round inguinal canal; above the artery of Sampson
Broad ligament
Connects: uterus, fallopian tubes, and ovaries to pelvic side wall
Contains: ovaries, fallopian tubes, round ligaments of uterus
Is a fold of the peritoneum
Ovarian ligament
Connects: medial pole of ovary to lateral uterus
Pathway of ejaculation
SEVEN UP: Seminiferous tubules Epididymis Vas deferens Ejaculatory ducts (Nothing) Urethra Penis
Autonomic innervation of the male sexual response
Erection: PSNS
Emission: SNS (hypogastric nerve)
Ejaculation: visceral and somatic nerves (pudendal nerve)
Spermatogonia
Germ cells
Line seminiferous tubules
Germ cell pool and produce 1° spermatocytes
Sertoli cells produce what?
Secrete inhibin B: inhibit FSH
Secrete androgen-binding protein: maintain local levels of testosterone
Produce MIF
What isolates gametes
from autoimmune attack?
Tight junctions between adjacent Sertoli cells
forming blood-testis barrier
Functions of sertoli cells?
Support and nourish developing spermatozoa
Regulate spermatogenesis
Function of leydig cells?
Secrete testosterone in the presence of LH
Ovulation
↑ estrogen, ↑ GnRH receptors on anterior pituitary
Estrogen surge then stimulates LH release: ovulation
What does APGAR stand for?
Appearance, Pulse, Grimace, Activity, Respiration
Definition of low birth weight
< 2500 g
Definition of menopause
amenorrhea for 12 months
Timeline of menopause
Amenorrhea for 12 months
Average age at onset is 51 years (earlier in smokers)
Preceded by 4–5 years of abnormal cycles
Hormonal changes seen in menopause
↓ estrogen, ↑↑ FSH, ↑ LH (no surge), ↑ GnRH
What causes aneuploidy?
Most commonly due to meiotic nondisjunction
Klinefelter syndrome
Testicular atrophy, eunuchoid body shape, tall, long extremities, gynecomastia, female hair distribution
Dysgenesis of seminiferous tubules: ↓ inhibin B leads to ↑ FSH
Abnormal Leydig cell function: ↓ testosterone -> ↑ LH -> ↑ estrogen
Turner syndrome
Short stature, ovarian dysgenesis (streak ovary), shield chest, bicuspid aortic valve, coarctation, lymphatic defects (result in webbed neck or cystic hygroma; lymphedema in feet, hands), horseshoe kidney
Menopause before menarche
Placental aromatase deficiency
Inability to synthesize estrogens from androgens
Masculinization of female infant
Maternal virilization during pregnancy
Androgen insensitivity syndrome
Defect in androgen receptor resulting in normal-appearing XY female; female external genitalia w/ functioning testes
5α-reductase de ciency
Ambiguous genitalia until puberty
Kallmann syndrome
Failure to complete puberty; a form of hypogonadotropic hypogonadism
Defective migration of GnRH-releasing neurons
Choriocarcinoma
Malignancy of trophoblastic tissue; no chorionic
villi present
Hematogenous spread to lungs: “cannonball”metastases
Placental abruption
Premature separation of placenta from uterine wall before delivery
Painful bleeding
Placenta accreta
Placenta attaches to myometrium without penetrating it; most common type
Placenta increta
placenta penetrates into myometrium
Placenta percreta
placenta penetrates (“perforates”) through myometrium and into uterine serosa (invades entire uterine wall);
Placenta previa
Attachment of placenta to lower uterine segment over (or < 2 cm from) internal cervical os
Painless bleeding
Vasa previa
Fetal vessels run over, or in close proximity to, cervical os
Postpartum hemorrhage
Tone (uterine atony; most common)
Trauma (lacerations, incisions, uterine rupture)
Thrombin (coagulopathy)
Tissue (retained products of conception)
Gestational hypertension
BP > 140/90 mm Hg after 20th week
Treatment of gestational HTN
Hydralazine, α-Methyldopa, Labetalol, Nifedipine; deliver by week 37-39
Preeclampsia
New-onset hypertension with either proteinuria or end-organ dysfunction after 20th week of gestation
Cause of preelampsia
Caused by abnormal placental spiral arteries: endothelial dysfunction, vasoconstriction, ischemia
Eclampsia
Preeclampsia + maternal seizures
HELLP syndrome
Hemolysis, Elevated Liver enzymes, Low Platelets.
D/t severe preeclampsia
Schisotcytes
Gynecologic tumor epidemiology
In US: endometrial > ovarian > cervical
Worldwide: cervical
Sarcoma botryoides
Embryonal rhabdomyosarcoma
Girls < 4 years old; spindle-shaped cells; desmin ⊕
Presents with clear, grape-like, polypoid mass emerging from vagina
HPV genes
E6 gene product (inhibits p53 suppressor gene)
E7 gene product (inhibits RB suppressor gene)
Serous cystadenoma
Benign ovarian neoplasm; most common
Lined with fallopian tube–like epithelium
Mucinous cystadenoma
Benign ovarian neoplasm
Multiloculated, large
Lined by mucus-secreting epithelium
Endometrioma
Endometriosis within ovary with cyst formation
Chocolate cyst
Mature cystic teratoma
Germ cell tumor, most common ovarian tumor in females 10–30 years old
Contains elements from all 3 germ layers
Brenner tumor
Looks like bladder
Solid tumor that is pale yellow-tan and appears encapsulated
Coffee bean” nuclei on H&E
Fibromas
Bundles of spindle-shaped fibroblasts
Meigs syndrome
triad of ovarian broma, ascites, hydrothorax
Thecoma
Like granulosa cell tumors, may produce estrogen
Abnormal uterine bleeding in a postmenopausal woman
Granulosa cell tumor
Malignant ovarian neoplasm
Women in their 50s
Call-Exner bodies (granulosa cells arranged haphazardly around collections of eosinophilic fluid, resembling primordial follicles)
Serous cystadenocarcinoma
Malignant ovarian neoplasm
Most common malignant ovarian neoplasm, frequently bilateral
Psammoma bodies
Mucinous cystadenocarcinoma
Malignant ovarian neoplasm
Pseudomyxoma peritonei–intraperitoneal accumulation of mucinous material from ovarian or appendiceal tumor
Immature teratoma
Malignant ovarian neoplasm
Aggressive, contains fetal tissue, neuroectoderm
Immature/embryonic-like neural tissue
Dysgerminoma
Most common in adolescents
Equivalent to male seminoma but rarer
Sheets of uniform “fried egg” cells
hCG, LDH: tumor markers
Yolk sac (endodermal sinus) tumor
Malignant ovarian neoplasms
Aggressive, in ovaries or testes and sacrococcygeal area in young children
Yellow, friable (hemorrhagic), solid mass
50% have Schiller-Duval bodies (resemble glomeruli)
AFP = tumor marker
Krukenberg tumor
GI malignancy that metastasizes to ovaries
Mucin-secreting signet cell adenocarcinoma
Endometrial polyp
Well-circumscribed collection of endometrial tissue within uterine wall
Painless abnormal uterine bleeding
Adenomyosis
Extension of endometrial tissue (glandular) into uterine myometrium; hyperplasia of basal layer of endometrium
Presents with dysmenorrhea, menorrhagia, uniformly enlarged, soft, globular uterus
Asherman syndrome
Adhesions and/or brosis of the endometrium
Leiomyoma (fibroid)
Multiple discrete tumors
Benign smooth muscle tumor
Estrogen sensitive
Whorled pattern of smooth muscle bundles with well-demarcated borders
Endometrial hyperplasia
Usually caused by excess estrogen stimulation
↑ risk for endometrial carcinoma
Endometrial carcinoma
Most common gynecologic malignancy
Presents with vaginal bleeding
Endometritis
Associated with retained products of conception following
Endometriosis
Non-neoplastic endometrium-like glands/stroma outside endometrial cavity
Fibrocystic changes in breast
Present with premenstrual breast pain or lumps; often bilateral and multifocal
Sclerosing adenosis
Type of fibrocystic change
Acini and stromal brosis, associated with calci cations
Epithelial hyperplasia of breast
Type of fibrocystic change
Cells in terminal ductal or lobular epithelium
↑ risk of carcinoma with
atypical cells
Fat necrosis of breast
Benign, usually painless, lump due to injury to breast tissue
Necrotic fat and giant cells on biopsy
Lactational mastitis
S aureus is most common pathogen
Treat with antibiotics and continue breastfeeding
Fibroadenoma
Small, well-de ned, mobile mass; benign
Estrogen sensitive
Intraductal papilloma
Small papillary tumor within lactiferous ducts, typically beneath areola; benign
Most common cause of nipple discharge
Phyllodes tumor
Large mass of connective tissue and cysts with “leaf-like” lobulations
Ductal carcinoma in situ
Noninvasive, malignant tumor
Fills ductal lumen
Early malignancy without basement membrane penetration
Comedocarcinoma
Noninvasive, malignant tumor
Ductal, central necrosis
Paget disease
Results from underlying DCIS or invasive breast cancer
Eczematous patches on nipple
Paget cells: intraepithelial adenocarcinoma cells
Invasive ductal carcinoma
Invasive, malignant tumor
Firm, brous, “rock-hard” mass with sharp margins and small, glandular, duct-like cells
Can deform suspensory ligaments: dimpling of skin
“Stellate” in ltration
Most common (∼ 75% of all breast cancers)
Invasive lobular carcinoma
Invasive, malignant tumor
Orderly row of cells (“single file”); ↓ E-cadherin expression
Medullary carcinoma
Invasive, malignant tumor
Fleshy, cellular, lymphocytic infiltrate
Good prognosis
Inflammatory breast cancer
Invasive, malignant tumor
Dermal lymphatic invasion by breast carcinoma
Peau d’orange
Poor prognosis
Peyronie disease
Abnormal curvature of penis due to fibrous plaque within tunica albuginea
Bowen disease
Precursor in situ lesion of penile SCC
Presents as leukoplakia in penile shaft
Erythroplasia of Queyrat
Precursor in situ lesion of penile SCC
cancer of glans, presents as erythroplakia
Bowenoid papulosis
Presents as reddish papules
Cryptorchidism
Undescended testis
↓ inhibin B, ↑ FSH, ↑ LH; ↓ testosterone in bilateral
Testicular torsion
Rotation of testicle around spermatic cord and vascular pedicle
Acute, severe pain, high-riding testis, and absent cremasteric reflex
Varicocele
Dilated veins in pampiniform plexus due to ↑ venous pressure
“Bag of worms” on palpation; augmented by Valsalva
Congenital hydrocele
Incomplete obliteration of processus vaginalis
Transilluminating swelling
Spermatocele
Cyst due to dilated epididymal duct or rete testis
Seminoma
Testicular germ cell tumor
Malignant; painless, homogenous testicular enlargement; most common
Large cells in lobules with watery cytoplasm and “fried egg” appearance
Similar to dysgerminoma in females
Yolk sac (endodermal sinus) tumor
Testicular germ cell tumor
Yellow, mucinous
Aggressive malignancy of testes, analogous to ovarian yolk sac tumor
Schiller- Duval bodies resemble primitive glomeruli
↑ AFP
Choriocarcinoma
Testicular germ cell tumor
Malignant, ↑ hCG
Disordered syncytiotrophoblastic and cytotrophoblastic elements
Hematogenous metas to lungs and brain
Embryonal carcinoma
Testicular germ cell tumor
Malignant, hemorrhagic mass with necrosis; painful
Glandular/papillary morphology
Leydig cell non–germ cell tumor
Golden brown color; contains Reinke crystals (eosinophilic cytoplasmic inclusions)
Produces androgens or estrogens
Sertoli cell non–germ cell tumor
Androblastoma from sex cord stroma
Testicular lymphoma
Most common testicular cancer in older men
Benign prostatic hyperplasia
Smooth, elastic, rm nodular enlargementof periurethral (lateral and middle) lobes, which compress the urethra
Prostatic adenocarcinoma
Arises most often from posterior lobe (peripheral zone)
Prostatic acid phosphatase (PAP) and PSA are useful tumor markers
Clomiphene
Antagonist at estrogen receptors in hypothalamus: inhibits neg feedback -> ↑ LH and FSH -> ovulation
Finasteride
Blocks 5α− reductase
BPH and male- pattern baldness
Androgen-receptor complex blockers (3)
Flutamide
Cyproterone
Spironolactone
Leuprolide
GnRH analog with agonist properties when given pulsatile
Downregulates GnRH receptor
Tamoxifen
Estrogen-r antagonist at breast; agonist at bone, uterus
ER/PR ⊕ breast cancer
Raloxifene
Estrogen-r antagonist at breast, uterus; agonist at bone
no increased risk of endometrial cancer
Aromatase inhibitors
Anastrozole, letrozole, exemestane
ER ⊕ breast cancer in postmenopausal women
Mifepristone, ulipristal
Competitive inhibitors of progestins at progesterone receptors
Abortion/ER contraception
Terbutaline, ritodrine
β2-agonists that relax the uterus
Danazol
Synthetic androgen that acts as partial agonist at androgen receptors
For: endometriosis, hereditary angioedema
Flutamide
Nonsteroidal competitive inhibitor at androgen receptors
Prostate carcinoma
Tamsulosin
α1-antagonist used to treat BPH by inhibiting smooth muscle contraction
Selective for α1A/D receptors (found on prostate) vs vascular α1B receptors
Minoxidil
Direct arteriolar vasodilator Androgenetic alopecia (pattern baldness), severe refractory hypertension
