197/198/199 - UG Development, Congenital Anomalies, Sexual Differentiation Flashcards
C - congenital adrenal hyperplasia due to 21-alpha-hydroxylase deficiency
- Testicular DSD will have male external genitalia
- In partial androgen insensitivity syndrome, gonads are present; will not have XX karyotype
Describe the presentation of posterior urethral valves
- Prenatal
- Bilateral hydronephrosis
- Thick-walled bladder
- Oligohydraminos
- Post-natal
- UTI
- Renal insufficiency
- Pulmonary insufficiency
- Incontinence
- Poor urinary stream
What is the role of sertoli cells in sexual differentiation?
Produce AMH -> regression of mullerian ducts
E - posterior urethral valves
Which primordial tissue gives rise to the kidney nephrons?
Metanephric mesoderm
Which indifferent-stage structure gives rise to the prostate and prostatic urethra in 46, XY individuals?
What is the corresponding structure in 46, XX individuals?
Urogenital sinus
Lower vagina and urethra in 46, XX individuals
Why is testosterone elevated in 21-alpha-hydroxylase deficiency?
Normally, 21-alpha-hydroxylase turns 17-OH-progesterone into 11-deoxycortisone
Without 21-alpha-hydroxylase, 17-OH-progesterone is shunted towards the testosteone synthesis pathway -> increaesed testosterone
In females, the secondary sex cords will give rise to which adult structure?
What kind of cells is this structure composed of?
Ovarian follicles
Ovum surrounded by epithelium of granulosa cells
Note: Primary sex cords persist as nonfunctional/vestigial rete ovarii
What is the most common congenital cystic kidney disease?
Multicystic dysplastic kidney
Where in the male is junction of the urethra derived from the urogenital sinus and surface ectoderm?
A. Urinary bladder and prostatic urethra
B. Beginning of the penile urethra
C. Proximal and distal halves of the penile urethra
D. Penile urethra and navicular fossa in the glans
E. Penile urethra and distal epidermis of the glans
D. Penile urethra and navicular fossa in the glans
Where in the adult female is the junction of derivatives of the paramesonephric ducts and urogenital sinus?
A. Uterine tubes and uterus
B. Uterine fundus and cervix
C. Uterus and vagina
D. Middle of the vagina
E. Vagina and vestibule
D. Middle of the vagina
Describe the internal and external genitalia that result from complete androgen insensitivity syndrome in a 46, XY individual
Testosterone present, but receptors non-functional
- Internal
- Testes, often undescended
- AMH secreted -> no uterus or Mullerian structures
- External
- No testosterone action -> female external genitalia
- Testosterone aromatized to estrogen -> breast development
- Often presents in a female-presenting individual with primary amenorrhea*
- 5-alpha-reductase deficiency will have female external genitalia but then development of male structures in puberty 2/2 increased testosterone*
In a ureteral duplication:
- Which ureter is more likely to develop obstruction?
- Which is more likely to develop reflux?
- Obstruction: Ureter from upper moiety
- Inserts inferiorly and medially in the bladder
- Also more likely to have ectopic ureter, ureterocele
- Reflux: Ureter from lower moiety
- Inserts laterally and superiorly in the bladder
- In general, this is more anatomically normal
Which 2 embryonic primordia form the male urethra?
- Urogenital sinus (endoderm) -> proximal majority
- Navicular fossa (ectoderm) -> distal end
Failure of fustion = hypospadias; opening on the ventral surface
A woman is infertile because of an absence of ova. Where might primordial ova have failed to differentiate?
A. Genital ridge mesoderm
B. Primary sex cords
C. Hindgut endoderm
D. Secondary sex cords
E. Paramesonephric duct
C. Hindgut endoderm
- Primordial germ cells orginate in the hindgut, then migrate to the genital ridge*
- Sex cords give rise to the epithelial components of the gonads only*
What is most common cause of ureteropelvic junction obstruction that is…
- Intrinsic:
- Extrinsic:
- Intrinsic: Aperistaltic segment
- Most common overall cause of UPJ
- Extrinsic: Crossing vessels
Which cells produce anti-mullerian hormone?
Sertoli cells
No gonads/streak gonad -> no Sertoli cells or Leydig cells -> no AMH or testosterone (respectively) -> Mullerian structures persist, no androgen effect on external genitalia
Fetal hydronephrosis 2/2 urinary tract dilation is detected on prenatal ultrasound
How should this be managed?
Observation
50-80% of antenatal hydronephrosis will spontaneously resolve; does not necessarily represent a specific pathology
What are the adult derivatives of the labioscrotal folds in…
- Males:
- Females:
- Males: Scrotum
- Females: Labia majora
C - complete androgen insensitivity syndrome
- 5-alpha reductase = no breast development
- Mixed gonadal dysgenesis is similar, but will not have symmetric inguinal masses (testes)
- 21-hydroxylase deficiency would present much earlier
- Salt wasting, hyperkalemia, failure to thrive soon after birth
Describe the internal and external genitalia that result from 5-alpha-reductase deficiency in a 46, XY individual
- Internal
- Testes, synthesize AMH -> no mullerian structures
- Also synthesize testosterone
- External
- Cannot convert testosterone to DHT -> Variable external genitalia
- Depends on amount of DHT that is produced
- More DHT -> more development of male structures
Male structures will often begin to develop during puberty due to increased testosterone
Where are sperm synthesized?
Where are they stored?
Synthesis: Testes
Storage: Epididymis
What embryonic structure gives rise to the ureter?
Mesonephric duct -> Ureteric bud
Keys is that the ureteric bud comes from the mesonephric duct, not the urogenital sinus
What causes mixed gonadal dysgenesis?
Mosaicism
One side has streak gonad, other has dysgenetic testicle
Most likely dx if testes are asymmetric
Which one of the following could persist as a cystic structure in the middle of the broad ligament of the uterus?
A. Urogenital sinus
B. Mesonephric duct
C. Allantois
D. Paramesonephric duct
E. Metanephric duct
B. Mesonephric duct
Remnant of the mesonephric duct - should only persist in male development
Which side is more susceptibel to ureteropelvic junction obstruction?
Left
(and M > F)
List the steps in the pathway that sperm take from the testes to the outside world
- Testes (synthesis → Epididymis (storage until ejaculation) → Vas deferens (aka ductus deferens → Inguinal canal → Seminal vesicles (picks up semen here) → Ejaculatory duct (after joining the prostatic urethra) → Membranous urethra → Penile urethra → Outside world
Extrophy of the bladder results from failure of mesoderm migration into which fetal structures?
failure of mesoderm migration into Cloacal membrane/ventral abdominal wall
What is the most common etiology of ureteropelvic junction obstruction that presents with intermittent flank pain?
Crossing vessel
Adynamic segment, high insertion, intrinsic narrowing would either be asymptomatic or constant
What is the fate of the primordial mesonephric duct? (4)
Male internal structures
- Seminal vesicles
- Epididymis
- Ejaculatory duct
- Ductus deferens (aka vas deferens)
- SEED*
- Note: Ureteric bud (-> ureters, pelvis, calyces, collecting duct) comes from the mesonephric duct*
What are the expected internal and external genitalia of a 46, XX individual with translocation of SRY?
(a 46, XX individual with presence of SRY)
- Internal
- Gonads are testicles; SRY contains gene that produces testes determing factor-> Stabilizes Wolffian structures
- External
- Male-appearing external genitalia
Which fetal nephrogenic cord derivative will eventually become the adult kidney?
Metanephros
Mesonephros is the first functioning kidney, then regresses
List 3 diagnoses that would result in a 46, XY individual with palpale testes and ambigious external genitalia
- 5-alpha-reductase deficiency
- Partial androgen insensitivity syndrome
- Congenital adrenal hypoplasia: low testosterone varity
- 3-beta-hydroxysteroid DH deficiency
- 17, 20 lyase deficiency
- 17-alpha-hydroxylase deficiency
Loss of function of which cells could result in persistent mulelrian duct syndrome?
(46, XY individual with a uterus and vagina)
Sertoli cells
They are supposed to produce anti-Mullerian hormone, which would cause regression of the Mullerian structures (vagina, uterus)
Describe the internal and external genitalia that result from complete gonadal dysgenesis in a 46, XY individual
- Internal
- No AMH -> Uterus present (but no ovaries; dysgenesis)
- No testosterone -> Wolffian structures regress (No male structures)
- External
- No testosterone -> female-typical external genitalia
No ovaries = no ovulation, but can carry a pregnancy
In a female, a gartner duct cyst results form failure of which embryonic structure to obliterate during development?
Mesonephric (Wolffian) duct
The mesonephric duct should obliterate; remnant = gartner duct cyst
Which embryonic structures give rise to:
- Germ cells:
- Gonadal epithelium:
- Germ cells: Hindgut
- Migrate into the genital ridge mesoderm, then are enveloped into the gonads
- Gonadal epithelium: Sex cords
- Male: primary sex cords -> seminiferous tubules (sertoli cells)
- Female: secondary sex cords -> ovarian follicles (granulosa cells)
What is the fate of the primordial paramesonephric duct? (3)
Female internal structures
- Fallopian tubes
- Uterus
- Upper 2/3 of the vajina
What is the gold standard for diagnosing vesicoureteral reflux?
Voiding systourethrogram (VCUG)
In males, the primary sex cords will give rise to which adult structure?
What kind of cells is this structure composed of?
Seminiferous tubules
Composed of epithelial sertoli cells
This is where sperm will develop
What are the adult derivatives of the urogenital folds in…
- Males:
- Females:
- Males: Ventral wall of the penis
- Females: Labia minora
Which of the following is the largest structure in the 8-week indifferent stage?
A. Mesonephros
B. Gonad
C. Metanephros
D. Urogenital sinus
E. Paramesonephric ducts
A. Mesonephros
What is the most common congenital cause of renal scarring?
How is it managed?
Vesicourethral reflux
- Medical: prevent UTI
- Surgery: lengthen intramural tunnel
- Reflex occus when the tunnel is short -> not enough pressure to keep the valve closed
Occurs when scarring and UTI are present
What are the adult derivatives of the ureteric buds? (4)
- Ureters
- Renal pelvis
- Calyces
- Collecting tubules in the pyramids
Note: Ureteric bud comes from mesonephric duct, not urogenital sinus
Which primordial structures give rise to the vagina? (2)
- Mullarian (paramesonephric) duct -> upper 2/3
- Urogenital sinus -> lower 2/3
When should an orchioplexy for an undescended testes (discovered at birth) be performed?
6 months of age
- May spontaneously descend (usually before 3 mo)
- Waiting until 6 mo decreases risks of general anesthesia
- Needs to be done in a “timely fashion”
Which differences of sexual development carry an increased risk of germ cell cancers? (3)
- Gonadal dysgenesis (partial and complete)
- Ovotesticular DSD
- Androgen insensitivity
No increased risk with 5-alpha reductase deficiency, SRY translocation in a 46, XX individual, or CAH
The urorectal septum divides the cloaca into which two structures?
What is the consequence if the division is incomplete?
Rectum and urogenital sinus
Incomplete division -> Fistula
What are the adult derivatives of the urogenital folds in…
- Males:
- Females:
- Males: Ventral wall of the penis
- Females: Labia minora
What are the adult derivatives of the urogenital sinus in…
- Males:
- Females:
- Males: Penile urethra
- Females: Vestibule
Which karyotypes are associated with ovotesticular DSD?
Any!
- Ovotestis may produce testosterone or estrogen (but more likely estrogen)
- Can produce sperm or eggs
- Decreased fertility, but may be able to have children
The primordia of the kidneys and gonads is…
- Somatopleure
- Intermediate mesoderm
- Splanchnopleure
b. Intermediate mesoderm
What is the first functioning kidney in fetal development?
Mesonephros
Will regress as the metanephros (final kidney) grows
Abnormal development of which structures results in hypospadias?
Failure of urethral plate to tubularize
(failure of urethral fold closure)
The primordia of the bladder and urethra is…
- Somatopleure
- Intermediate mesoderm
- Splanchnopleure
c. Splanchnopleure
The primordia of the genitals is…
- Somatopleure
- Intermediate mesoderm
- Splanchnopleure
a. Somatopleure
Which cells convert testosterone to DHT during development?
Which enzyme?
Leydig cells
5-alpha-reductase
Potent DHT stabilizes male sexual structures during development
Why should undescended testes be repaired with orchiopexy?
(What is the most serious possible sequelae?)
No repair = increased risk of seminoma
