Built from Repro Lecture 04 (LOs 1–4). Close notes. Fill from memory. Reveal only after a genuine attempt.

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)

Testes originate near what organ? (Shared embryologic origin)

Structure that guides descent

Gestational month when descent completes, and what hormone triggers gubernacular contraction

Scrotal temperature vs core; why does this matter?

Cryptorchidism (LO1)

Most common congenital GU anomaly in males? Rate in term vs preterm

Classic lab pattern: T, LH, FSH, inhibin B

Why is testosterone NORMAL but inhibin B LOW? (Which cells are heat-resistant vs heat-sensitive?)

Most feared long-term consequence + classic tumor type

Timing of orchidopexy

Pampiniform plexus & varicocele (LO1)

Pampiniform plexus — structure + physiologic function

Drainage pattern: R testicular vein → ? | L testicular vein → ?

Varicocele — classic exam finding; which side predominates and why (anatomy)

Clinical RED FLAG varicocele (2 scenarios) → what cancer must you rule out?

Testicular torsion vs epididymitis (LO1)

Feature	Torsion	Epididymitis
Onset
Prehn sign (elevation relieves pain?)
Cremasteric reflex
Doppler flow
Management

Surgical window to save torsed testis

"Bell-clapper deformity" — what is it and why does it predispose to torsion?

Epididymitis pathogens: young men vs older men

Three tunicas (outside → in) (LO1)

Layer (outside → in)	Histology	Clinical / HY
Tunica vaginalis (outermost)
Tunica albuginea (middle)
Tunica vasculosa (innermost)

Leydig vs Sertoli cells (LO1)

Feature	Leydig cells	Sertoli cells
Location
Pituitary hormone that regulates it
Main secretion(s)
Feedback inhibitor of its gonadotropin
Characteristic histologic feature
Heat sensitivity

Sertoli-cell secretion that KEEPS intratubular T ~100× plasma level

Sertoli-cell secretion in FETAL life that regresses Müllerian ducts

Local enzyme in Sertoli cells that converts T → estradiol

DHT conversion: enzyme + why DHT matters (potency)

Blood-testis barrier (LO1)

Formed by what junctions between what cells?

Two compartments it creates; which cell types live in each?

Why is the barrier needed immunologically? (What antigens are "new"?)

Disruption scenarios (3) that can cause anti-sperm antibodies

Sertoli-cell-only (Del Castillo) syndrome — lab pattern + semen finding

HPG axis — fill each row (LO1)

Hormone	Target cell	Effect	Feedback inhibitor
LH
FSH
Testosterone

Primary testicular failure pattern (T / LH / FSH / inhibin B)

Hypothalamic-pituitary failure pattern (Kallmann, pit adenoma)

Anabolic steroid use pattern (T / LH / testis size / gyneco)

Sertoli-cell-only pattern (T / LH / FSH)

Spermatogenesis — fill each stage (LO1)

Cell	Ploidy / DNA	Stage	Compartment
Spermatogonium (type A / B)
Primary spermatocyte
Secondary spermatocyte
Spermatid
Spermatozoon

Total duration of spermatogenesis in the tubule

Additional maturation time in the epididymis

How many mature spermatozoa per 1 spermatogonium? (vs oogenesis?)

Why do cohorts develop synchronously (mechanism)?

Spermiogenesis — 5 remodeling events (LO1)

1. Formation of ____ (cap over nucleus; hyaluronidase + acrosin)

2. Nuclear condensation — histones replaced by ____

3. Flagellum — what microtubule arrangement forms from the centriole?

4. Midpiece — what wraps the axoneme? What does it power?

5. Cytoplasm elimination — what are the discarded fragments, and who phagocytoses them?

Sperm anatomy — fill each region (LO1)

Region	Contents	Function
Head
Neck
Midpiece
Principal piece
End piece

Kartagener syndrome: defect + classic triad (3 features)

LO 2

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)

Tubulus rectus — epithelium + function

Rete testis — where is it located? What epithelium?

Why "intratesticular" matters: what's the role of both segments?

Efferent ductules (LO2)

Approximate number of ductules + where they connect

Embryologic origin (and why it's important for their FUNCTION)

Two epithelial cell types + what each does

Pathognomonic luminal appearance on histology

Primary physiologic role (what % of fluid is reabsorbed?)

Epididymis (LO2)

Length + shape

Epithelium — specific type + what's on the apical surface

Trap: are stereocilia true cilia? Why not? (axoneme)

Two functions of the epididymis

Region	Function	Sperm state
Head (caput)
Body (corpus)
Tail (cauda)

Vas deferens & vasectomy (LO2)

Epithelium + defining histologic feature

Three muscular layers (inside → out)

Nerve driving ejaculatory peristalsis

Vasectomy: why does testosterone stay normal?

Vasectomy: why does ejaculate volume stay ~normal?

Why is backup contraception needed for 2–3 months post-vasectomy?

Two potential complications (granuloma; immune)

Ampulla & ejaculatory duct (LO2)

Where is the ampulla anatomically? What's its role?

How is the ejaculatory duct formed? Where does it empty?

Verumontanum / seminal colliculus — what is it + what opens there?

Distinguishing ducts on histology — master table (LO2)

Structure	Epithelium	Luminal contour	Muscular layer	Key clue
Tubulus rectus
Rete testis
Efferent ductules
Epididymis
Vas deferens

LO 3

ON EXAM — ejaculate: seminal vesicles ~70% + FRUCTOSE, prostate ~25% + PSA (cleaves semenogelin), Cowper's <5%; CBAVD + CFTR + no fructose; 4 prostate zones (BPH = transition; cancer = peripheral, osteoblastic mets to lumbar spine); BPH Rx (tamsulosin α1 + finasteride 5α-RI); Cowper's = mucus gland SURROUNDED BY SKELETAL MUSCLE; erection Point (PSNS/NO/cGMP) & Shoot (SNS/T10–L2); sildenafil + nitrates = hypotension

Ejaculate composition (LO3)

Source	% Volume	Key contents	Function
Seminal vesicles
Prostate
Bulbourethral (Cowper's)
Epididymis + vas

Seminal vesicles (LO3)

Location; where does each empty?

Classic histologic appearance (mucosa shape + pigment?)

Sperm storage site? (trap)

Role of FRUCTOSE in semen analysis (what does absent fructose suggest?)

CBAVD — what does it stand for, what gene, and what 2 findings on semen analysis?

Prostate zones & histology (LO3)

Zone	% of gland	Classic pathology
Peripheral zone
Central zone
Transition zone
Anterior fibromuscular stroma

Corpora amylacea — what are they + clinical significance?

"Two-cell layer" on histology — what loss supports invasive cancer? (markers)

PSA — what enzyme class + physiologic job?

Four prostate secretions besides PSA

What androgen specifically drives prostate growth?

BPH vs prostate cancer (LO3)

Feature	BPH	Prostate Cancer
Zone
Symptoms
DRE finding
Histology (cell layers)
Labs
Treatment

Most common cancer in men? How it metastasizes (pattern + classic site)?

Gleason score — what is it?

4 classes of androgen-deprivation drugs for advanced prostate cancer

How does finasteride affect PSA? Clinical relevance?

Bulbourethral (Cowper's) glands (LO3)

Size + location

Pathognomonic histology — what muscle surrounds them?

Three functions of the secretion

Female homologue + embryologic origin

Penis — structure & erection (LO3)

Three erectile bodies (name + how many)

Which erectile body contains the urethra?

Which erectile body(ies) is/are primary for rigidity? Why do they trap blood well?

Why does the corpus spongiosum remain compressible during erection?

Erection vs ejaculation (Point & Shoot) (LO3)

Mnemonic: Point = Parasympathetic (erection); Shoot = Sympathetic (emission/ejaculation).

Phase	Autonomic branch + nerve roots	Transmitter / Mechanism
Erection
Emission
Ejaculation (somatic expulsion)

PDE5 inhibitors — name 3 + mechanism

PDE5 + nitrates — what happens and why?

Priapism — definition + 3 common causes + why it's an emergency

3 causes of autonomic-driven ED

LO 4

ON EXAM — 3 segments + epithelium (Prostatic = transitional/urothelium; Membranous = pseudostratified/stratified columnar; Penile = same w/ stratified squamous near meatus); internal sphincter smooth α1 (retrograde ejaculation trap) vs external sphincter skeletal pudendal; membranous = SHORTEST + pelvic fracture site; straddle = bulbous; epithelium predicts malignancy (proximal = urothelial CA, distal = SCC); blood at meatus → retrograde urethrogram BEFORE catheter

Two sphincters (LO4)

Feature	Internal urethral sphincter	External urethral sphincter
Muscle type
Voluntary?
Innervation
Key role

Retrograde ejaculation (LO4)

Mechanism: which sphincter fails and why?

Classic presentation (ejaculate + urine findings)

4 causes (drug + neuropathy + surgery)

Why doesn't tamsulosin cause urinary incontinence?

Three urethral segments — master table (LO4)

Segment	Length	Epithelium	Surrounding structure	Unique landmark / clinical
Prostatic
Membranous
Penile (spongy)

Verumontanum — location + what opens here + significance of the prostatic utricle

Glands of Littré — what are they and where?

Fossa navicularis — location + epithelium

Urethral trauma & obstruction (LO4)

Pelvic fracture → which urethral segment? Why?

Straddle injury → which urethral segment? Classic perineal finding?

4 red-flag signs suggesting urethral injury (that stop you from catheterizing)

Next step when urethral injury is suspected? Alternative drainage?

Posterior urethral valves (PUV) — what, who, consequence chain

Urethral strictures — 3 causes

Urethritis (LO4)

Type	Organism(s)	Clinical clue
Gonococcal urethritis
Non-gonococcal urethritis (NGU)

Empiric urethritis treatment (covers both)

Reactive arthritis (Reiter) — classic triad + HLA + trigger

Epithelium predicts malignancy: proximal urethra → ? | distal urethra → ?

LO 1–4 · USMLE Step 1 Style

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.

Male Reproductive System — Active Recall