Hub 1 — Core Concepts

Urogenital System I & II Active Drills

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Lecture 02 · Repro Block · Urogenital Embryology — Urinary & Genital Development
Primary: RPD02 Lecture Guide (HoyaDocs)
Lecturer: Embryology
Review: Langman's Medical Embryology Ch. 16
Step 1: First Aid Repro — Embryology
Hub Progression: Hub 1 — Core Concepts → →
16
Flashcards
10
Fill-in-Blank
3
Ordering Drills
3
Match Sets
8
Test Traps
Click a card to flip · 16 cards totalUrogenital Embryology
Germ Layers
From which germ layer does the majority of the urogenital system derive? Name three exceptions.
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Answer
Intermediate mesoderm gives rise to most of the urogenital tract.

Exceptions:
• Adrenal medulla → ectoderm (neural crest)
• Genital swellings → ectoderm
• Urogenital sinus → endoderm
Pseudo-Kidneys
Name the three kidney precursors in chronological order, their timing, and which one makes urine.
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Answer
Pronephros — start of week 4 (neck region); does NOT form urine; regresses by end of wk 4.

Mesonephros — end of wk 4 through wk 10; forms urine (glomerulus-like filtration); drains into cloaca.

Metanephros — week 5; becomes the definitive kidney; starts making urine at week 10.
Reciprocal Induction
What two structures signal each other to form the definitive kidney, and what does each contribute?
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Answer
Ureteric bud (from mesonephric duct) ↔ metanephric blastema (from intermediate mesoderm) — each induces the other to grow.

Metanephros → NEPHRON: Bowman's capsule, PCT, LOH, DCT, cortex & medulla.
Ureteric bud → COLLECTING system: collecting duct, minor/major calyces, renal pelvis, ureter.
Kidney Ascent
When do the kidneys ascend, what blocks them from ascending if fused, and what's the final adult arterial supply?
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Answer
Kidneys ascend just before nephrons develop (after ureteric bud bifurcates).

If fused (horseshoe kidney), ascent is blocked by the IMA (inferior mesenteric artery).

Final supply: abdominal aorta (renal arteries). Persistent accessory vessels → anatomical variation.
Cloaca Splitting
What divides the cloaca? What two cavities result, and what does each become?
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Answer
The urorectal septum divides the cloaca starting at week 4 (~day 30).

Anterior → urogenital sinus → primitive bladder, urethra, lower vagina/prostatic urethra.
Posterior → anorectal canal → rectum & anal canal.
Trigone Origin
What forms the smooth trigone of the bladder, and why is this embryological origin different from the rest of the bladder?
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Answer
The mesonephric (Wolffian) ducts get absorbed into the developing bladder during weeks 5–6, forming the vesical trigone — a triangular smooth region containing the openings of the ureters and urethra.

The rest of the bladder is derived from endoderm (urogenital sinus), so the trigone is mesodermal in origin while the bladder dome is endodermal.
SRY Gene
What does SRY encode, and which cells secrete MIS vs. testosterone in the developing testis?
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Answer
SRY (on Y chromosome) codes for TDF (Testis Determining Factor).

Sertoli cells (from primitive sex cords) → MIS/AMH → regresses Müllerian ducts.

Leydig cells (weeks 8–10) → testosterone → maintains Wolffian ducts.

Testosterone → DHT via 5α-reductase → masculinizes external genitalia.
Duct Fates
What do the mesonephric (Wolffian) and paramesonephric (Müllerian) ducts become in males vs. females?
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Answer
Wolffian (mesonephric) duct:
• ♂ → "SEED": Seminal vesicles · Epididymis · Ejaculatory duct · Ductus (vas) deferens (+ trigone)
• ♀ → degenerates (remnants = Gartner's duct cysts)

Müllerian (paramesonephric) duct:
• ♂ → degenerates (MIS from Sertoli)
• ♀ → fallopian tubes, uterus, cervix, upper 2/3 vagina
DHT — External Genitalia
What does DHT do to external genital primordia in males? What happens in females without DHT?
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Answer
DHT present (♂):
• Genital tubercle → glans/shaft of penis
• Urogenital (urethral) folds → fuse ventrally → penile urethra
• Labioscrotal swellings → fuse midline → scrotum (with raphe)

DHT absent (♀ default):
• Tubercle → clitoris
• Urethral folds → labia minora (unfused)
• Labioscrotal swellings → labia majora (unfused)
Potter Sequence
What is the pneumonic "POTTER," what causes it, and why is it usually fatal?
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Answer
POTTER: Pulmonary hypoplasia · Oligohydramnios · Twisted face · Twisted skin · Extremity defects · Renal failure

Causes: bilateral renal agenesis, polycystic kidney disease, obstructive uropathy, VACTERL defects (esophageal atresia → can't swallow amniotic fluid).

Lethal from pulmonary hypoplasia — lungs can't mature without amniotic fluid (fetal urine makes amniotic fluid in T2).
Horseshoe Kidney
What is a horseshoe kidney, where does it get stuck, and what is the classic imaging association?
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Answer
Lower poles of both kidneys fuse in the midline (both metanephric blastemas meet near midline). The U-shaped organ tries to ascend but gets trapped under the IMA.

Usually asymptomatic; found incidentally on prenatal US or CT/MRI/IVP. ↑ association with Turner syndrome and ↑ risk of UTI, nephrolithiasis, renal cancer.
MCDK
What causes Multicystic Dysplastic Kidney (MCDK), how is it different from ADPKD, and what's its prognosis?
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Answer
MCDK: abnormal interaction between ureteric bud & metanephric blastema during initial kidney development → non-functioning cysts replace normal tissue.

Unilateral: usually asymptomatic — contralateral kidney compensates.
Bilateral: incompatible with life (Potter sequence).

Differs from ADPKD: MCDK is a developmental sporadic defect; ADPKD is genetic (PKD1/PKD2), presents in adulthood with hypertension and renal failure.
Hypospadias vs Epispadias
What fails in hypospadias? In epispadias? Which is more common and which is associated with bladder exstrophy?
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Answer
Hypospadias (more common) — urethral folds fail to fuse → abnormal urethral opening on the ventral (inferior) shaft of penis. Most defects are distal (glanular, subcoronal).

Epispadias — faulty positioning of genital tubercle → opening on the dorsal (superior) side. Associated with bladder exstrophy.

Treat with urethroplasty (buccal mucosa graft) around 6–12 months.
Cryptorchidism
What is cryptorchidism, when is orchidopexy performed, and why does timing matter?
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Answer
Failure of testicular descent through the inguinal canal into the scrotum. Guided by the gubernaculum.

If not descended by 6 months → orchidopexy.

Early surgery lowers risk of:
• Seminoma (testicular malignancy)
• Infertility (heat-sensitive spermatogenesis)
• Inguinal hernia

Also → ↓risk of torsion & improves cosmesis.
21-Hydroxylase Deficiency (CAH)
Why does 21-hydroxylase deficiency virilize XX females? What electrolytes/BP findings are classic?
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Answer
95% of CAH cases. 21-OH is needed for aldosterone & cortisol — when blocked, precursors shunt to androgens (testosterone, DHT).

In XX: excess androgens → virilized/ambiguous genitalia.

Labs: ↓aldosterone → salt wasting, hyponatremia, hyperkalemia, hypotension; ↑17-OH-progesterone (screening marker); ↓cortisol → hypoglycemia.

Contrast: 11β-OH def → HTN (desoxycortico­sterone buildup). 17α-OH def → HTN + no virilization (XX appears phenotypically normal, XY looks female).
5α-Reductase Deficiency vs AIS
How do 5α-reductase deficiency and complete androgen insensitivity differ at puberty and in hormone levels?
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Answer
5α-reductase deficiency (46 XY):
• Testosterone normal, ↑T:DHT ratio
• Female/ambiguous external genitalia at birth
• At puberty, ↑testosterone → virilization ("penis at 12")
• Internal male structures present (Wolffian derivatives)

Complete AIS (46 XY):
• Defective androgen receptor
• Normal/↑ testosterone + ↑ LH
• Female external genitalia, blind vagina
• No Müllerian derivatives (MIS still produced)
• At puberty → breast development (peripheral aromatization); amenorrhea
• Gonadectomy AFTER puberty (↑malignancy risk)
FIB 01 — Germ Layers
The majority of the urogenital system is derived from the ___________ mesoderm. The adrenal ___________, however, is derived from ectoderm (neural crest).
Hint: Paraxial / Intermediate / Lateral plate — which one is in the middle?
FIB 02 — Kidney Precursors
The ___________ appears at week 4 and does not form urine. The ___________ appears at end of week 4 and filters until week 10. The ___________ develops at week 5 and becomes the definitive kidney.
Hint: Think cranial-to-caudal sequence.
FIB 03 — Reciprocal Induction
The metanephric ___________ gives rise to the NEPHRON (Bowman's capsule, PCT, LOH, DCT). The ureteric ___________ gives rise to the COLLECTING system (collecting ducts, calyces, renal pelvis, ureter).
Hint: Both structures signal each other to grow — one becomes the filter, the other becomes the plumbing.
FIB 04 — Cloaca Split
At week 4, the ___________ septum divides the cloaca. The anterior portion becomes the urogenital ___________, which forms the primitive bladder. The posterior portion becomes the ___________ canal.
FIB 05 — Trigone Formation
During weeks 5–6, the ___________ ducts are absorbed into the developing bladder, forming the smooth triangular ___________ — a region of mesodermal origin in an otherwise endodermal bladder.
FIB 06 — Sexual Differentiation
The ___________ gene on the Y chromosome encodes Testis Determining Factor. Sertoli cells secrete ___________ (MIS), which regresses the Müllerian ducts. Leydig cells secrete ___________ from week 8.
FIB 07 — DHT
Testosterone is converted to the more potent ___________ (DHT) by the enzyme ___________. DHT masculinizes the external genitalia; testosterone alone maintains internal male ducts.
FIB 08 — Potter Sequence
Failure of fetal urine production causes ___________ (low amniotic fluid), leading to pulmonary ___________ (the cause of death). Fetal compression also produces classic flattened facies and extremity defects.
Hint: "POTTER" mnemonic — the first letter of each.
FIB 09 — CAH
The most common form of CAH (95%) is ___________-hydroxylase deficiency, which presents with salt wasting, hyponatremia, hyperkalemia, and ___________ (BP finding) due to aldosterone deficiency. The screening marker is elevated ___________-progesterone.
Hint: Contrast with 11β-OH deficiency → HTN.
FIB 10 — Testicular Descent
The testes descend through the inguinal canal guided by the ___________. Failure of this descent = ___________. If undescended by 6 months, an ___________ is performed to reduce the risk of infertility and seminoma.
Instructions: Drag and drop the items into the correct order, then click "Check Order." Use "Show Answer" if you get stuck.
Drill 1 — Kidney Development: Chronological Order
Arrange these 5 kidney embryology milestones from earliest to latest.
⠿Ureteric bud bifurcates → renal pelvis + calyces form (wk 6–7)
⠿Mesonephros forms urine; mesonephric duct drains into cloaca (wk 4–10)
⠿Nephrons (Bowman's, PCT, LOH, DCT) form; metanephros starts making urine (wk 8–10)
⠿Pronephros appears in neck region (start of wk 4) — non-functional
⠿Ureteric bud sprouts from mesonephric duct → meets metanephric blastema (wk 5)
  1. Pronephros — wk 4 neck; transient, non-functional
  2. Mesonephros — wk 4 end → wk 10; filters urine into cloaca
  3. Ureteric bud + metanephric blastema — wk 5; reciprocal induction
  4. Ureteric bud bifurcation — wk 6–7; renal pelvis & calyces
  5. Nephron formation — wk 8–10; metanephros becomes the definitive kidney
Drill 2 — Male External Genitalia Formation (under DHT)
Arrange these 6 steps in the correct order of male external genital development.
⠿Labioscrotal swellings fuse at midline → scrotum (with visible raphe)
⠿Leydig cells secrete testosterone (wk 8–10)
⠿Epithelial invagination at glans forms external urethral meatus
⠿SRY gene → TDF → primitive sex cords form Sertoli cells
⠿5α-reductase converts testosterone → DHT
⠿Genital tubercle elongates; urethral folds fuse ventrally → penile urethra
  1. SRY → TDF → Sertoli cells — also secrete MIS (regresses Müllerian)
  2. Leydig cells secrete testosterone — maintains Wolffian ducts
  3. 5α-reductase — testosterone → DHT (required for external genitalia)
  4. Genital tubercle + urethral fold fusion → penis shaft + penile urethra
  5. Labioscrotal swellings fuse → scrotum (raphe marks fusion line)
  6. Urethral meatus — epithelial invagination at glans
Drill 3 — Bladder/Urethra Formation from Cloaca
Arrange the 5 steps of bladder development from cloaca to final structure.
⠿Mesonephric ducts absorbed into bladder wall → vesical trigone (wk 5–6)
⠿Urorectal septum divides cloaca → anterior urogenital sinus + posterior anorectal canal
⠿Middle sinus → female urethra OR male prostatic + membranous urethra; bottom sinus → lower vagina (♀) or penile urethra (♂)
⠿Cloaca is single common chamber for urinary, genital, and GI tracts (through wk 4)
⠿Top of urogenital sinus expands → primitive bladder
  1. Single cloaca — through week 4
  2. Urorectal septum divides — anterior UG sinus / posterior anorectal canal
  3. Top of UG sinus → primitive bladder
  4. Mesonephric ducts absorbed → trigone — wk 5–6 (mesodermal, unlike rest of bladder dome)
  5. Middle/bottom sinus → urethra + lower vagina/penile urethra
Instructions: Click an item on the left, then click its match on the right. Correct pairs turn green; wrong pairs flash red.
Set 1 — Embryologic Origin → Adult Structure
Match each embryonic precursor to its adult derivative.
Embryonic Precursor
Ureteric bud
Metanephric blastema
Mesonephric (Wolffian) duct (♂)
Paramesonephric (Müllerian) duct (♀)
Adult Structure
Fallopian tubes, uterus, upper 2/3 vagina
Ureter, renal pelvis, calyces, collecting ducts
Seminal vesicles, epididymis, ejaculatory duct, vas deferens
Nephron (Bowman's, PCT, LOH, DCT)
Score: 0/4 correct
Set 2 — Male ↔ Female Homologous Structures
Match each male structure to its female embryologic homolog.
Male Structure
Glans/shaft of penis
Scrotum
Cowper's (bulbourethral) glands
Prostate / prostatic utricle
Gubernaculum
Female Homolog
Bartholin's (greater vestibular) glands
Round ligament of uterus + ovarian ligament
Clitoris
Skene's glands (prostatic utricle ↔ vagina/uterus)
Labia majora
Score: 0/5 correct
Set 3 — Congenital Urogenital Anomaly → Underlying Defect
Match each anomaly to the embryologic failure that produces it.
Anomaly
Horseshoe kidney
Multicystic Dysplastic Kidney (MCDK)
Ectopic ureter
Hypospadias
Underlying Defect
Urethral folds fail to fuse → ventral urethral opening on penis
Metanephric blastemas fuse at midline; ascent blocked by IMA
Incomplete/abnormal mesonephric duct absorption into bladder
Abnormal interaction of ureteric bud and metanephros during initial development
Score: 0/4 correct
Test Trap Mode: Each statement is either TRUE or FALSE as written. Many are designed to catch common exam errors. Click T or F — then read the explanation carefully.
Trap 01 — Germ Layers
"The entire adrenal gland is derived from intermediate mesoderm, just like the rest of the urogenital system."
FALSE. Only the adrenal cortex is from intermediate mesoderm. The adrenal medulla is derived from neural crest (ectoderm) — it is chromaffin tissue that secretes catecholamines. Remember: "GFR = Salty, Sweet, Sexy" for the cortex; medulla = modified sympathetic ganglion.
Trap 02 — Nephron vs Collecting
"The ureteric bud gives rise to the glomerulus, Bowman's capsule, and proximal convoluted tubule."
FALSE. Reversed! The metanephric blastema (mesoderm) → NEPHRON (Bowman's capsule, PCT, LOH, DCT). The ureteric bud (outgrowth of the mesonephric duct) → COLLECTING system (collecting duct, calyces, renal pelvis, ureter). They meet via reciprocal induction.
Trap 03 — Horseshoe Kidney
"A horseshoe kidney is usually found in the pelvis because the IMA (inferior mesenteric artery) prevents its ascent."
FALSE (partly). A horseshoe kidney is typically NOT in the pelvis — it's stuck at a lower-than-normal position (around L3–L4) because the IMA blocks further ascent. A pelvic kidney (a different anomaly) is an unascended unilateral kidney that stays in the pelvis. Don't conflate the two. Horseshoe is also linked with Turner syndrome.
Trap 04 — Müllerian Ducts
"In the default (female) pathway, the Müllerian ducts regress and the Wolffian ducts form the upper 2/3 of the vagina."
FALSE. Completely reversed. In females (no MIS, no testosterone), the Wolffian ducts regress and the Müllerian ducts persist → fallopian tubes, uterus, cervix, upper 2/3 of vagina. Lower 1/3 of vagina comes from the urogenital sinus (endoderm).
Trap 05 — DHT Targets
"Testosterone (not DHT) is responsible for masculinization of the external genitalia in utero."
FALSE. DHT (not testosterone) masculinizes the external genitalia (penis, scrotum, prostate). Testosterone maintains the internal male ducts (Wolffian derivatives — epididymis, vas, seminal vesicle, ejaculatory duct). This is why 5α-reductase deficiency produces an XY with female-appearing external genitalia but normal internal male structures.
Trap 06 — CAH BP
"All forms of congenital adrenal hyperplasia (CAH) cause hypotension due to mineralocorticoid deficiency."
FALSE. BP depends on WHICH enzyme is deficient: 21-OH def (95%) → ↓aldosterone → hypotension, salt wasting; 11β-OH def → 11-deoxycorticosterone buildup (weak mineralocorticoid) → HYPERtension; 17α-OH def → ↑mineralocorticoids → HYPERtension + absence of sex hormones.
Trap 07 — Potter Sequence
"Potter sequence babies die from renal failure shortly after birth because their kidneys cannot excrete waste."
FALSE. The cause of death in Potter sequence is pulmonary hypoplasia → respiratory failure — NOT renal failure. Fetal urine makes amniotic fluid (in T2); oligohydramnios prevents lung maturation. The babies have no kidneys OR non-functioning kidneys (bilateral MCDK, PKD, obstructive uropathy), but the lungs are what fail first.
Trap 08 — Cryptorchidism Treatment
"Orchidopexy for cryptorchidism is typically delayed until after puberty to allow maximum testicular growth."
FALSE. Orchidopexy should be performed by 6 months of age (or no later than 12 months). Delay ↑ risk of infertility (heat-sensitive spermatogenesis) and seminoma/germ cell tumors. In contrast, complete AIS requires gonadectomy AFTER puberty (different indication — undescended testes produce estradiol that drives puberty).
Kidney Precursors — Timing & Function
StructureTimingFunctionFate
PronephrosStart of week 4 (neck)Non-functional; nephric duct + nephrotomesRegresses end of wk 4
MesonephrosEnd of wk 4 → wk 10Produces urine; drains into cloaca via mesonephric (Wolffian) ductDuct persists in ♂ (SEED derivatives + trigone)
MetanephrosWeek 5 onwardsDefinitive kidney; begins making urine at wk 10Becomes the permanent kidney
Ureteric budSprouts wk 5 from WolffianInduces metanephric blastema; branches repeatedlyForms COLLECTING system (CD, calyces, pelvis, ureter)
Metanephric blastemaMesoderm near mesonephric ductInduced by ureteric budForms NEPHRON (Bowman's, PCT, LOH, DCT)
UG Tract Derivatives — Male vs Female
OriginFemale DerivativeMale Derivative
Ureteric budUreter, calyces, pelvis, CDUreter, calyces, pelvis, CD
Mesonephric (Wolffian) ductTrigone of bladder (absorbed); degenerates otherwise (Gartner's duct cyst)Trigone + SEED: Seminal vesicles, Epididymis, Ejaculatory duct, Ductus (vas) deferens
Paramesonephric (Müllerian) ductFallopian tubes, uterus, cervix, upper 2/3 vaginaDegenerates (MIS from Sertoli); remnant = appendix testis, prostatic utricle
Urogenital sinusBladder (except trigone), entire urethra, lower 1/3 vagina, Bartholin's + Skene's glandsBladder (except trigone), prostatic + membranous urethra, prostate, bulbourethral (Cowper's) glands
Genital tubercleClitorisGlans/shaft of penis
Urogenital foldsLabia minora (unfused)Penile urethra (fused ventrally)
Labioscrotal swellingsLabia majora (unfused)Scrotum (fused with raphe)
GonadOvaryTestis
Urinary Tract Developmental Anomalies
AnomalyCauseClinical Pearls
MCDK (Multicystic Dysplastic)Abnormal ureteric bud / metanephric blastema interactionUnilateral → usually asymptomatic; bilateral → Potter sequence (fatal)
Horseshoe kidneyMetanephric blastemas fuse at midline → ascent blocked by IMALies lower than normal; ↑ risk UTI, stones, Wilms'; assoc. Turner syndrome
Pelvic kidneyFailure of ascent (unilateral)Usually asymptomatic; adrenal stays at normal site (separate origin)
Ureteral duplicationAbnormal ureteric bud bifurcationComplete (2 ureters) vs incomplete/bifid (fuse before bladder)
Ectopic ureterIncomplete absorption of mesonephric duct into bladderGirls: dribbling + normal voiding (drains below ext. sphincter); often with duplex kidney (upper pole)
UPJ obstructionBlockage where renal pelvis meets ureterMost common cause of hydronephrosis in newborns
UreteroceleCystic dilation of distal ureter into bladder"Cobra head" sign on imaging; often with duplicated system
Posterior urethral valves (♂)Abnormal folds in prostatic urethraMost common cause of bladder outlet obstruction in male infants; oligohydramnios
Disorders of Sexual Differentiation — Hormone Pattern
ConditionKaryotypeInternal GenitaliaExternal PhenotypeKey Hormones
Complete AIS46 XYNo Müllerian (MIS); Wolffian regresses (no AR signal)Female, blind vagina, no pubic hair↑ testosterone, ↑ LH, ↑ estradiol (aromatized)
5α-reductase def46 XYNormal Wolffian (epididymis, vas)Female/ambiguous at birth → virilizes at pubertyNormal T, ↑ T:DHT ratio
21-OH def (CAH)46 XX (classic)Normal MüllerianVirilized/ambiguous; salt-wasting crisis↑ 17-OH-progesterone, ↑ androgens, ↓ aldo, ↓ cortisol
11β-OH def (CAH)46 XXNormal MüllerianVirilized + HTN↑ 11-deoxycorticosterone, ↑ androgens
17α-OH def (CAH)XY or XXAmbiguous/femaleXY: female phenotype; XX: normal but no 2° sex char. at puberty; HTN + hypoK↑ mineralocorticoids, ↓ sex hormones, ↓ cortisol
Klinefelter (XXY)47 XXYInternal male (T+MIS present)Male with tall stature, gynecomastia, small testes↑ LH/FSH, ↓ T, ↑ estradiol (aromatase)
Turner (XO)45 XOStreak ovariesShort, webbed neck, ovarian failure, horseshoe kidney, coarctation↑ LH/FSH, ↓ estrogen
Key principle: In any 46 XY with external "female" or ambiguous genitalia, always ask — is testosterone normal (AIS)? Is DHT normal (5α-reductase deficiency)? Are Müllerian structures present (MIS status)? These three data points isolate the defect.