Plus: what's the one-line "SEVEN UP" mnemonic for this pathway?
Testis & Spermatogenesis
Excurrent Ducts
Accessory Glands & Penis
Male Urethra
Practice Qs
LO 1
ON EXAM — cryptorchidism labs (normal T, low inhibin B, high FSH), left varicocele / "bag of worms" / new RIGHT varicocele = RCC, torsion vs epididymitis (Prehn sign, cremasteric reflex, 6-hour window), tunicas V-A-V, Leydig (LH + Reinke crystals + tubular cristae) vs Sertoli (FSH + ABP + inhibin B + MIS + blood-testis barrier), 74-day spermatogenesis, spermiogenesis 5 steps, 9+2 axoneme + Kartagener
Testicular descent (LO1)
Near the kidneys — same intermediate mesoderm origin as the urogenital tract
GUBERNACULUM — guides descent through inguinal canal into scrotum
Month 7 of gestation; fetal androgens (testosterone/DHT) trigger GUBERNACULAR CONTRACTION that pulls testes down
Scrotum ~34°C vs core 37°C — spermatogenesis requires cooler temperature (Sertoli + germ cells are heat-sensitive; Leydig are heat-resistant)
Cryptorchidism (LO1)
MOST COMMON congenital GU anomaly in males — ~3% term, ~30% preterm
T = NORMAL | LH = normal/high | FSH = HIGH | inhibin B = LOW — isolated FSH elevation
Leydig cells are HEAT-RESISTANT (T stays normal). Sertoli + germ cells are HEAT-SENSITIVE → ↓ inhibin B → loss of selective FSH feedback → FSH rises; spermatogenesis impaired
↑ Risk of GERM CELL TUMORS — classically SEMINOMA in an abdominal testis; risk persists even after orchidopexy
Orchidopexy BEFORE 1 year of age (after 6-month observation for spontaneous descent)
Pampiniform plexus & varicocele (LO1)
Dense venous plexus surrounding the testicular artery within the spermatic cord → COUNTERCURRENT HEAT EXCHANGE (cools warm arterial blood before it reaches the testis)
Right testicular vein → IVC (at acute angle) | Left testicular vein → LEFT RENAL VEIN (at 90° angle)
LEFT-sided ~90% ("bag of worms" on exam) because the left testicular vein enters the left renal vein at a right angle → ↑ backpressure → plexus dilation
NEW right-sided varicocele OR a left varicocele that does NOT decompress supine → evaluate for RENAL CELL CARCINOMA invading the renal vein / IVC
Testicular torsion vs epididymitis (LO1)
Feature
Torsion
Epididymitis
Onset
SUDDEN, severe (adolescents 12–18); predisposed by bell-clapper deformity
Gradual (hours to days); often with dysuria or STI history
Prehn sign (elevation relieves pain?)
NEGATIVE — elevation does NOT relieve pain
POSITIVE — elevation RELIEVES pain
Cremasteric reflex
ABSENT
Preserved
Doppler flow
↓ or absent flow
↑ flow (inflammation)
Management
Surgical EMERGENCY — detorsion + bilateral orchiopexy within 6 hours
Antibiotics (GC/Chlamydia young; E. coli / coliforms older) + scrotal support + NSAIDs
Within 6 hours to preserve the testis (complete ischemia beyond this)
Abnormally free testis within the tunica vaginalis (horizontal lie) → predisposes to twisting around the spermatic cord; typically bilateral → hence bilateral orchiopexy
Young men: Chlamydia trachomatis + Neisseria gonorrhoeae | Older men: E. coli, Pseudomonas, other coliforms
Three tunicas (outside → in) (LO1)
Layer (outside → in)
Histology
Clinical / HY
Tunica vaginalis (outermost)
Single layer of mesothelial (simple cuboidal) cells — visceral + parietal layers from processus vaginalis
Meiotic + haploid germ cells express NEW surface antigens not present at fetal immune tolerance → would be recognized as foreign without the barrier → prevents autoimmune orchitis
(1) Vasectomy (sperm antigen leakage); (2) Testicular trauma; (3) Mumps orchitis — any can produce anti-sperm antibodies
Sertoli-cell-only (Del Castillo) syndrome — tubules contain ONLY Sertoli cells (no germ cells); AZOOSPERMIA + isolated ↑↑ FSH, normal LH, normal T
HPG axis — fill each row (LO1)
Hormone
Target cell
Effect
Feedback inhibitor
LH
Leydig cells
Testosterone synthesis (cAMP-PKA → StAR → cholesterol pathway)
Testosterone (own negative feedback on LH and GnRH)
FSH
Sertoli cells
Support spermatogenesis; secrete ABP + inhibin B + MIS; convert T → estradiol
INCOMPLETE CYTOKINESIS during mitosis/meiosis leaves cytoplasmic bridges between sister germ cells → synchronous development of cohorts
Spermiogenesis — 5 remodeling events (LO1)
ACROSOME — Golgi-derived cap over the nucleus; contains hydrolytic enzymes (hyaluronidase + acrosin) for penetrating corona radiata + zona pellucida during fertilization
ON EXAM — SEVEN UP pathway, efferent ductules = scalloped border + mesonephric origin, epididymis = pseudostratified columnar with STEREOCILIA (NOT cilia — no 9+2), vas = thick 3-layer muscle around small lumen, vasectomy physiology (2–3 months to clear; T + ejaculate unaffected), verumontanum = where ejaculatory ducts open into prostatic urethra
Tubulus rectus & rete testis (LO2)
Short, straight transitional tubules; simple CUBOIDAL epithelium (Sertoli-free); direct exit from seminiferous tubule into rete testis
Located in the MEDIASTINUM TESTIS (posterior testicular CT); anastomosing network; simple cuboidal ± occasional microvilli/cilia
Both are INTRATESTICULAR — they collect sperm-containing fluid from ALL seminiferous tubules and funnel it into a single route toward the efferent ductules
Efferent ductules (LO2)
~20 small ducts connecting the rete testis to the HEAD (caput) of the epididymis
Derived from MESONEPHRIC TUBULES (same origin as kidney tubules) — retain strong fluid/solute-reabsorbing capability
(1) TALL CILIATED cells — beat to move sperm toward epididymis; (2) SHORT NON-CILIATED RESORPTIVE cells — reabsorb fluid
"SCALLOPED" or "toothed" luminal border — alternating tall + short cells produce the signature pattern
Reabsorb ~90% of testicular fluid → dramatically CONCENTRATE sperm before they enter the epididymis
Epididymis (LO2)
~7 meters, highly coiled, single duct on the posterior testis
PSEUDOSTRATIFIED COLUMNAR with STEREOCILIA (long, non-motile microvilli); contains principal cells (absorption + secretion) + basal cells (progenitors)
NO — stereocilia are LONG MICROVILLI (actin-based, non-motile, no 9+2 axoneme). True cilia (respiratory tract, oviduct, efferent ductules) have a 9+2 arrangement and are motile via dynein
(1) Sperm MATURATION (gain motility + fertilizing capability via epididymal secretions); (2) Sperm STORAGE (up to ~1 month in the tail)
Progressive maturation; continued absorption + secretion
Sperm gaining motility
Tail (cauda)
Wider lumen slows fluid → STORAGE
Sperm fully mature; can fertilize; stored ~1 month
Vas deferens & vasectomy (LO2)
Pseudostratified columnar with STEREOCILIA (similar to epididymis, often shorter); defining feature = disproportionately THICK muscular wall around small stellate lumen
Sympathetic (hypogastric plexus, T10–L2) → peristaltic contraction during emission phase of ejaculation
Leydig cells are in the testicular interstitium — not affected by cutting the duct. LH/T feedback remains intact → T stays normal
~70% of ejaculate is seminal vesicle fluid, ~25% prostate — none affected by vasectomy. Sperm-free ejaculate looks the same in volume
Residual mature sperm DISTAL to the ligation (in the ampulla, seminal vesicles, ejaculatory duct) must clear — takes ~2–3 months / ~20 ejaculations. Semen analysis confirms azoospermia before discontinuing backup
Dilated distal end of the vas deferens, located behind the bladder; MIXING site where sperm meets accessory gland secretions
Formed by union of vas ampulla + seminal vesicle duct; ~2 cm long; passes through the prostate and empties onto the VERUMONTANUM of the prostatic urethra
VERUMONTANUM (seminal colliculus) — midline posterior prominence of the prostatic urethra; EJACULATORY DUCTS open here (flanking the prostatic utricle, a Müllerian remnant)
Distinguishing ducts on histology — master table (LO2)
Paired glands posterior to the bladder; each empties into the ipsilateral vas deferens to form the ejaculatory duct
Highly folded / labyrinthine mucosa = "HONEYCOMB" appearance on histology; pseudostratified/simple columnar epithelium; lipofuscin pigment (golden-brown) accumulates with age
NO — seminal vesicles are NOT a sperm storage site. Sperm transit through but are not stored here
Absent fructose → suggests EJACULATORY DUCT OBSTRUCTION or CONGENITAL ABSENCE OF SEMINAL VESICLES (often seen with CBAVD)
CBAVD = Congenital Bilateral Absence of the Vas Deferens; associated with CFTR mutations. Often paired with absent seminal vesicles → LOW EJACULATE VOLUME + ABSENT FRUCTOSE + obstructive azoospermia
Prostate zones & histology (LO3)
Zone
% of gland
Classic pathology
Peripheral zone
~70% of prostate
~70% of PROSTATE CANCERS (posterior; palpable on DRE)
Central zone
~25% of prostate
~5% of cancers
Transition zone
~5% in young males (expands with age)
BPH ARISES HERE → compresses urethra → obstructive urinary symptoms
Anterior fibromuscular stroma
~0% glandular (all stromal)
No glands → no cancer
CORPORA AMYLACEA — small, round, eosinophilic, concentrically laminated calcified bodies in prostatic lumina; increase with age; benign signature but NOT diagnostic of cancer
Normal/BPH has TWO-cell epithelium (inner luminal + outer basal). Prostate adenocarcinoma = LOSS of basal cell layer (confirmed on p63 or HMWCK immunostain)
PSA (prostate-specific antigen) = serine protease that cleaves semenogelin to liquefy the semen coagulum; clinical biomarker for BPH and prostate cancer
Active surveillance (low risk); radical prostatectomy; radiation; ANDROGEN DEPRIVATION (GnRH agonists like leuprolide; AR antagonists like bicalutamide/enzalutamide; abiraterone CYP17i)
MOST COMMON CANCER IN MEN; 2nd most common cause of cancer death. Spreads via OSTEOBLASTIC bone metastases (vs most cancers which are osteolytic) — classic lumbar spine + pelvis
(1) Neutralize urethral acidity (protect sperm from residual acidic urine); (2) Lubricate the urethra before ejaculation; (3) Shield urethra from destructive enzymes in ejaculate
Female homologue = BARTHOLIN'S (greater vestibular) glands; both derived from the urogenital sinus
Penis — structure & erection (LO3)
Three erectile bodies: paired CORPORA CAVERNOSA (2) + single CORPUS SPONGIOSUM (1)
Corpus SPONGIOSUM contains the penile (spongy) urethra; extends distally to form the glans penis
Corpora CAVERNOSA provide primary rigidity — surrounded by rigid TUNICA ALBUGINEA that traps blood by compressing emissary veins against it
Corpus spongiosum has a THINNER tunica albuginea → remains compressible during erection so the urethra stays patent for ejaculation
Erection vs ejaculation (Point & Shoot) (LO3)
Mnemonic: Point = Parasympathetic (erection); Shoot = Sympathetic (emission/ejaculation).
Phase
Autonomic branch + nerve roots
Transmitter / Mechanism
Erection
PARASYMPATHETIC — S2–S4 pelvic splanchnic nerves
Release ACh + NO (nitric oxide) → NO activates guanylate cyclase → ↑ cGMP → smooth muscle relaxation → helicine artery dilation → sinusoid engorgement → emissary veins compressed against tunica albuginea → blood trapped → erection
Emission
SYMPATHETIC — hypogastric nerves (T10–L2)
Peristalsis of epididymis, vas deferens, accessory glands → semen delivered into the prostatic urethra; internal urethral sphincter contracts to prevent retrograde flow
Ejaculation (somatic expulsion)
SOMATIC — pudendal nerve (S2–S4)
Bulbospongiosus + ischiocavernosus muscles contract to expel semen out of the urethra (voluntary + reflex)
SILDENAFIL, tadalafil, vardenafil — inhibit PDE5 (enzyme that breaks down cGMP) → prolonged smooth-muscle relaxation → sustained erection
Nitrates produce NO → ↑ cGMP; PDE5i prevents cGMP breakdown. COMBINATION = severe vasodilation → life-threatening HYPOTENSION + MI. ABSOLUTE contraindication
Prolonged erection (>4 hours) — urologic emergency; risk of permanent ED if untreated. Causes: PDE5-inhibitor overuse, SICKLE CELL disease, trazodone
Tamsulosin blocks α1-mediated INTERNAL sphincter tone (smooth muscle) — but the EXTERNAL sphincter is SKELETAL muscle controlled by the pudendal nerve (not α1) — so urinary continence is preserved
Urogenital diaphragm; encircled by EXTERNAL URETHRAL SPHINCTER (skeletal muscle)
Shortest segment; most common site of TRAUMATIC RUPTURE in pelvic fractures
Penile (spongy)
~15 cm (LONGEST segment)
Pseudostratified/stratified columnar; STRATIFIED SQUAMOUS non-keratinized near meatus (fossa navicularis)
Corpus spongiosum
GLANDS OF LITTRÉ (mucus glands); Cowper's (bulbourethral) duct openings
Midline prominence on the posterior wall of the prostatic urethra; EJACULATORY DUCTS open here. PROSTATIC UTRICLE (blind pouch between openings) is a Müllerian-duct REMNANT — analogous to uterus/upper vagina in females
Small mucus-secreting glands along the wall of the penile (spongy) urethra; lubricate during passage of ejaculate
Dilated distal portion of the penile urethra, just proximal to the external urethral meatus; lined by STRATIFIED SQUAMOUS non-keratinized epithelium (transitioning to keratinized glans skin)
Urethral trauma & obstruction (LO4)
Pelvic fracture disrupts the MEMBRANOUS urethra — it's the shortest, narrowest, and most fixed segment (passes through urogenital diaphragm); pelvic diastasis shears it
(1) Blood at urethral meatus; (2) Inability to void; (3) Perineal bruising; (4) HIGH-RIDING PROSTATE on DRE (displaced superiorly from urethral discontinuity)
Obtain a RETROGRADE URETHROGRAM before any catheterization (blind catheter can worsen tear + create false passage). If urgent bladder drainage is needed → SUPRAPUBIC CYSTOSTOMY bypasses the urethra
Posterior Urethral Valves — congenital mucosal flaps in the PROSTATIC urethra of male infants → severe bladder outlet obstruction → bilateral hydronephrosis → oligohydramnios (Potter sequence); fatal without intervention
8 questions — cover all 4 LOs. Use these after finishing all tabs.
Q1. A 28-year-old man with a history of unilateral cryptorchidism that underwent orchidopexy at age 8 presents with infertility. Semen analysis shows azoospermia. Labs: testosterone 420 ng/dL (normal), LH 9 mIU/mL (normal-high), FSH 28 mIU/mL (high), inhibin B 20 pg/mL (low). Which ONE cell population is MOST directly responsible for the pattern of isolated FSH elevation?
A. Leydig cells — heat-damaged → loss of testosterone → ↑ LH
B. Sertoli cells — heat-damaged → loss of inhibin B → ↑ FSH
C. Spermatogonia — directly suppress LH by paracrine signaling
D. Myoid cells around the tubule produce inhibin B
E. Pituitary gonadotrophs are intrinsically damaged by heat
B — Heat-damaged Sertoli cells → ↓ inhibin B → loss of selective FSH negative feedback. Leydig cells are heat-RESISTANT, so testosterone stays normal and LH is only mildly elevated. Sertoli cells (and germ cells) are heat-SENSITIVE: damage → ↓ inhibin B, which is the specific negative-feedback inhibitor of FSH → FSH rises in isolation. Late orchidopexy (age 8) did not prevent the damage — intervention before age 1 preserves more fertility. Cancer surveillance is still required (↑ seminoma risk persists).
Q2. A 35-year-old man presents with a left-sided scrotal mass that feels like a "bag of worms" and decompresses when he lies supine. Which venous drainage anomaly BEST explains the left-sided predominance of this finding?
A. The left testicular vein drains into the IVC at an acute angle
B. The right testicular vein drains into the left renal vein at a right angle
C. The left testicular vein drains into the left renal vein at a 90° angle → ↑ backpressure
D. Left-sided varicoceles are caused by congenital absence of the pampiniform plexus
E. The cremasteric artery is shorter on the left
C — Left testicular vein drains into the left renal vein at 90° → ↑ backpressure → dilation of the pampiniform plexus. ~90% of varicoceles are left-sided for this reason. The RIGHT testicular vein drains directly into the IVC at an acute angle (less resistance). A new RIGHT-sided varicocele — or a left varicocele that does NOT decompress supine — should raise concern for renal cell carcinoma invading the renal vein/IVC and occluding drainage.
Q3. A pathologist examines a prostate biopsy and reports small, crowded glands with prominent nucleoli and a single layer of cells (no basal layer identified on p63 or HMWCK staining). Corpora amylacea are visible in adjacent benign-appearing glands. Which of the following BEST explains the pathologist's conclusion?
A. BPH — the missing basal layer is a hyperplasia artifact
B. Prostatitis — acute inflammation obscures the basal cells
C. Prostatic adenocarcinoma — loss of the basal cell layer supports invasion
D. Granulomatous prostatitis after BCG therapy
E. Normal prostatic histology
C — Prostate adenocarcinoma. Loss of the basal cell layer is a hallmark of invasion. Normal and benign (BPH) prostatic glands have a TWO-cell epithelium — inner luminal secretory + outer basal. Pathologists confirm the basal layer with p63 or HMWCK (high-molecular-weight cytokeratin). Absence of basal cells + small crowded glands + prominent nucleoli → adenocarcinoma. Cancer typically arises in the PERIPHERAL zone (vs BPH in the TRANSITION zone). Corpora amylacea are age-related benign inclusions — they sit in neighboring glands but don't confer malignancy.
Q4. A 42-year-old man with infertility, bilateral absence of the vas deferens on palpation, and an ejaculate volume of 0.4 mL with ABSENT fructose undergoes genetic testing. Which mutation is MOST likely, and what is the embryologic link explaining the low volume and absent fructose?
A. AR mutation — Wolffian derivatives never form without androgen signaling
B. SRY mutation — testes don't form, so no ducts form
C. CFTR mutation — CBAVD with associated hypoplastic seminal vesicles (Wolffian-duct derivatives)
D. 5α-reductase deficiency — external genitalia defects but normal ducts
E. Kallmann syndrome — hypothalamic GnRH deficiency
C — CFTR mutation → Congenital Bilateral Absence of the Vas Deferens (CBAVD). CFTR mutations cause fetal obstruction/atresia of the developing vas deferens. Because the vas and seminal vesicles are both derived from the mesonephric (Wolffian) duct, seminal vesicles are often absent or hypoplastic as well. Seminal vesicles contribute ~70% of ejaculate volume AND are the sole source of fructose — so CBAVD classically presents with low-volume, fructose-negative azoospermic ejaculate. Leydig function (and testosterone) is preserved. Management: testicular sperm extraction + ICSI; genetic counseling for the partner.
Q5. A 17-year-old boy presents to the ED with sudden, severe right-sided testicular pain that began 3 hours ago while playing basketball. On exam, the right testis is high-riding and transverse, the cremasteric reflex is absent, and elevation of the scrotum does NOT relieve pain. Doppler US shows absent flow to the right testis. What is the MOST appropriate next step?
A. Start ceftriaxone + doxycycline empirically
B. Schedule outpatient urology follow-up within 48 hours
C. Emergent surgical detorsion with bilateral orchiopexy
D. Give IV antibiotics and observe for 24 hours
E. MRI pelvis to confirm the diagnosis
C — Emergent surgical detorsion + bilateral orchiopexy. Classic testicular torsion: sudden onset, high-riding/transverse testis, absent cremasteric reflex, negative Prehn sign (elevation does NOT help), and absent Doppler flow. This is a surgical emergency — the 6-hour window is key; delay risks ischemic infarction. Bilateral orchiopexy is done because the predisposing "bell-clapper deformity" is typically bilateral. Epididymitis (A) would have positive Prehn, preserved cremasteric reflex, and INCREASED Doppler flow.
Q6. A pathologist identifies a male reproductive duct whose luminal epithelium has a characteristic "scalloped" or "toothed" appearance from alternating tall ciliated and short non-ciliated cells. What structure is this, and what is its embryologic origin?
A. Rete testis; intermediate mesoderm
B. Epididymis; mesonephric duct
C. Efferent ductules; mesonephric tubules
D. Vas deferens; mesonephric duct
E. Seminal vesicle; urogenital sinus
C — Efferent ductules, derived from mesonephric TUBULES. The "scalloped" or "toothed" border is the pathognomonic visual feature of efferent ductules. The tall ciliated cells move sperm toward the epididymis; the short non-ciliated cells reabsorb ~90% of testicular fluid, concentrating sperm. The mesonephric-tubule origin (same as kidney tubules) is why they retain strong fluid-resorptive capacity. The vas deferens and epididymis come from the mesonephric DUCT (not tubules) and have smooth pseudostratified columnar epithelium with stereocilia.
Q7. A 68-year-old man with BPH on tamsulosin and diabetic autonomic neuropathy reports that his ejaculate volume has dropped to almost nothing, and his post-coital urine is cloudy. Which structure and mechanism BEST explain this finding?
A. External urethral sphincter dysfunction → urinary incontinence
B. Internal urethral sphincter fails to close → retrograde flow of semen into the bladder
C. Seminal vesicles atrophy from chronic α1 blockade
D. Prostatic ductal obstruction from BPH
E. Pelvic floor weakness from aging
B — Retrograde ejaculation — internal urethral sphincter fails to close during emission. During normal emission, sympathetic α1 tone closes the internal urethral sphincter at the bladder neck, directing semen forward. Tamsulosin (selective α1A antagonist) blocks this — AND diabetic autonomic neuropathy further impairs sympathetic function — so semen flows backward into the bladder. Orgasm is preserved; post-coital urinalysis shows sperm, confirming the diagnosis. The external urethral sphincter (skeletal, pudendal-controlled) is unaffected → urinary continence is preserved.
Q8. A 30-year-old man is brought to the ED after a motorcycle accident with a displaced pelvic fracture. He is unable to void, and blood is visible at the urethral meatus. DRE reveals a high-riding prostate. The urology resident wants to place a Foley catheter. What is the next appropriate step, and which urethral segment is MOST likely disrupted?
A. Place the Foley immediately; the membranous urethra is resilient to trauma
B. Obtain a retrograde urethrogram; the membranous urethra is most vulnerable to pelvic fractures
C. CT cystogram; the prostatic urethra usually ruptures in pelvic trauma
D. Suprapubic cystostomy only; never image urethra in trauma
E. Attempt a small-caliber catheter under fluoroscopic guidance
B — Retrograde urethrogram; pelvic fractures classically disrupt the MEMBRANOUS urethra. The membranous urethra is the SHORTEST, narrowest, and most fixed segment — it traverses the urogenital diaphragm, so pelvic fractures that disrupt the diaphragm shear it. Red-flag signs are present: blood at meatus + high-riding prostate + inability to void. Blind catheterization risks converting a partial tear into a complete one. Always do retrograde urethrogram first; if urgent bladder drainage is needed, use suprapubic cystostomy. Contrast this with straddle injury (perineum against a bike crossbar) → bulbous urethra rupture + "butterfly" perineal bruising.