Difficulty: Intermediate | Prerequisites: Sex determination and differentiation notes, gametogenesis and HPG axis notes
This is the applied physiology of the male reproductive system. You already know how the system is built (differentiation) and how it is switched on (puberty and the HPG axis). This topic covers the working machinery: the anatomy of the male tract, how testes are kept at the right temperature, the detailed cellular process of spermatogenesis, the hormones that regulate it, the composition of semen, and the physiology of erection and ejaculation. It finishes with the clinically relevant endpoints: erectile dysfunction, andropause, and puberty disorders. This is where the basic science meets the exam questions.
The male reproductive system is built for continuous sperm production and delivery. Spermatogenesis occurs in the seminiferous tubules, supported by Sertoli cells and driven by testosterone from Leydig cells, within a tightly temperature-controlled environment. Accessory glands contribute 99% of semen volume. Erection is a vascular event under parasympathetic control; ejaculation is a two-phase process under sympathetic and somatic control. Disorders include erectile dysfunction, puberty timing abnormalities and age-related decline (andropause).
Seminiferous tubules
The coiled tubes within the testis where spermatogenesis occurs. Contain Sertoli cells and developing germ cells.
Think of them as the production floor of the sperm factory.
Sertoli cells
"Nurse cells" found within the seminiferous tubules. They surround and support developing sperm, form the blood-testis barrier, and produce key regulatory substances including inhibin, activin, ABP and luminal fluid.
Leydig cells
Cells in the interstitial tissue between seminiferous tubules. They produce testosterone in response to LH.
Think of them as the hormone factory sitting alongside the sperm factory.
Blood-testis barrier (BTB)
A physical barrier formed by tight junctions between adjacent Sertoli cells. It separates the basal compartment (containing spermatogonia) from the adluminal compartment (containing more mature germ cells), preventing immune cells and antibodies from reaching developing sperm.
In simple terms, it stops your immune system from attacking your own sperm, which it would otherwise recognise as foreign.
Spermatocytogenesis
The first phase of spermatogenesis: mitotic proliferation of spermatogonia followed by meiotic reduction division to produce spermatids.
Spermiogenesis
The second phase: morphological transformation of round spermatids into streamlined spermatozoa. Includes acrosome formation, chromatin condensation, loss of excess cytoplasm and tail formation. No cell division occurs.
Spermiation
The final phase: release of mature spermatozoa from Sertoli cells into the lumen of the seminiferous tubule.
Androgen-binding protein (ABP)
A protein produced by Sertoli cells that binds testosterone and maintains high local testosterone concentrations within the seminiferous tubules.
Epididymis
A coiled duct on the posterior surface of the testis where sperm mature, gaining motility and fertilising capacity. Transit takes approximately 12 days.
Pampiniform plexus
A network of veins surrounding the testicular artery. Acts as a countercurrent heat exchanger, cooling arterial blood before it reaches the testis.
Cryptorchidism
A condition in which one or both testes fail to descend from the abdominal cavity into the scrotum. Results in elevated testicular temperature and infertility if uncorrected.
Varicocele
Abnormal enlargement of the pampiniform plexus veins. Can raise testicular temperature and impair spermatogenesis.
Erectile dysfunction (ED)
Inability to achieve or sustain a penile erection sufficient for sexual intercourse.
Phosphodiesterase-5 (PDE-5)
An enzyme that breaks down cyclic GMP (cGMP) in penile smooth muscle. PDE-5 inhibitors (such as sildenafil/Viagra) block this enzyme, prolonging the vasodilatory effect of cGMP and supporting erection.
Andropause
An age-related decline in testosterone levels in men. Controversial in definition; affects roughly 50% of men over 50 years old, though spermatogenesis often continues.
Precocious puberty
Onset of sexual maturation before age eight. May be true (with normal HPG axis activation and gametogenesis) or pseudo (secondary characteristics only, without gametogenesis, due to abnormal hormone exposure).
Delayed puberty
Absence of expected pubertal milestones: no menses by age 17 in females, or no testicular development by age 20 in males.
Testes:
Paired organs housed in the scrotum (outside the body cavity for temperature regulation)
Contain seminiferous tubules (site of spermatogenesis) and interstitial tissue (site of testosterone production)
Internal genitalia:
Seminiferous tubules
Epididymis (sperm maturation)
Vas deferens / ductus deferens (sperm transport)
External genitalia:
Penis
Scrotum
Common passage: urethra (shared by reproductive and urinary systems)
Accessory glands and ducts:
Prostate gland: buffers, citric acid, enzymes
Seminal vesicles: fructose (energy for sperm), vitamin C, prostaglandins; their secretions promote uterine contractions that aid sperm transport
Bulbourethral glands (Cowper's glands): mucus and buffers
Spermatogenesis requires a temperature approximately 1°C below core body temperature. Deviation from this optimal range causes infertility.
Four mechanisms maintain the correct temperature:
Testes housed outside the body in the scrotum
Scrotal sweat glands
Pampiniform plexus (countercurrent venous heat exchanger around the testicular artery)
Tunica dartos and cremaster muscles (adjust the position of the testes relative to the body: contract in cold to draw testes closer, relax in heat to let them hang lower)
Pathologies of temperature control:
Cryptorchidism: testes remain in the abdominal cavity; descend normally during the third trimester. Causes infertility if uncorrected.
Fever, tight underwear and hot working environments can all impair spermatogenesis
Varicocele: abnormal dilation of the pampiniform plexus, disrupting the heat exchange mechanism
Location: seminiferous tubules of the testes
Duration: approximately 65 to 70 days per cycle; a new cycle starts every two to three weeks, so multiple stages overlap
Continues from: puberty until death
Three phases:
1. Spermatocytogenesis
Mitosis: spermatogonia proliferate
Meiosis I: primary spermatocytes divide into secondary spermatocytes (reduction division, 46 chromosomes to 23)
Meiosis II: secondary spermatocytes divide into spermatids (haploid)
2. Spermiogenesis
Morphological differentiation of spermatids into spermatozoa (no further cell division)
Key changes:
Acrosome formation (contains enzymes essential for fertilisation)
Chromatin condensation
Loss of excess cytoplasm
Tail (flagellum) formation
Mitochondrial spiral develops in the mid-piece (provides energy for motility)
3. Spermiation
Release of mature spermatozoa from Sertoli cells into the tubule lumen
At release, sperm are immotile
They are suspended in Sertoli cell fluid
Propelled through the tubules by cilia and myoid cell contractions
Sperm then enter the epididymis for final maturation (gaining motility)
Head: contains the nucleus (haploid DNA) and acrosome (enzyme-filled vesicle for penetrating the egg)
Mid-piece: packed with mitochondria arranged in a spiral, providing ATP for flagellar movement
Tail (flagellum): composed of microtubules; provides motility
The tight junctions between Sertoli cells divide the tubule into three compartments:
Tubule lumen: where mature sperm are released
Adluminal compartment: contains spermatocytes and spermatids undergoing meiosis and differentiation
Basal compartment: contains spermatogonia (stem cells)
The interstitial tissue outside the tubules contains:
Leydig cells (testosterone production)
Capillaries (nutrient delivery and waste removal)
Formed by tight junctions between Sertoli cells
Prevents antibodies and immune cells from crossing into the adluminal compartment
Prevents sperm antigens from reaching the systemic immune system
Without this barrier, the body would mount an immune response against its own sperm (autoimmune infertility)
Also controls the chemical environment around developing sperm (selective passage of proteins, steroids, glucose, potassium)
Hormonal control:
GnRH (hypothalamus) stimulates LH and FSH (anterior pituitary)
LH acts on Leydig cells, producing testosterone
FSH acts on Sertoli cells, stimulating their support functions
Testosterone and inhibin exert negative feedback on GnRH, LH and FSH
Sertoli cell functions (important, frequently tested):
Target for both FSH and testosterone
Feed and support developing spermatozoa
Produce luminal fluid
Produce inhibin (suppresses FSH) and activin (stimulates FSH)
Produce oestrogens (limited amounts, via aromatase)
Produce androgen-binding protein (ABP), maintaining high local testosterone
Produce plasminogen activator (forms plasmin, needed for spermiation)
Create and maintain the blood-testis barrier
Testosterone:
The most important androgen
Synthesised by Leydig cells under the influence of LH
Circulates in the blood: approximately 3% free (biologically active), approximately 97% bound to sex steroid-binding globulin (SSBG) or androgen-binding protein (ABP)
Converted in peripheral tissues to:
DHT (via 5-alpha reductase), which is biologically more potent than testosterone
Androstenedione
17-beta oestradiol (via aromatase, in small amounts)
Main androgens in males: testosterone and DHT
Functions of androgens:
Anabolic effects: protein synthesis, erythropoiesis, bone growth
Androgenic effects: development and maintenance of the reproductive system
Secondary sex characteristics (body and facial hair, deep voice, male body shape, muscle mass, fat distribution)
Spermatogenesis
Libido and sexual behaviour
Note: anabolic steroids (synthetic androgens) are used illegally by athletes to enhance performance
Small amounts are produced by aromatisation of testosterone in Sertoli cells and fat cells
Sertoli cell oestrogen production increases ABP synthesis, which reduces free testosterone levels locally
The relationship between oestrogen and ABP is important
Inhibin: produced by Sertoli cells; decreases FSH via negative feedback
Activin: produced by Sertoli cells; increases FSH via positive feedback
Both work specifically on FSH (since FSH is the gonadotrophin that activates Sertoli cells, this creates a local regulatory loop)
Accessory glands contribute approximately 99% of semen volume. The vaginal pH is very acidic, so semen must buffer and protect sperm.
Component | Function | Source |
|---|---|---|
Sperm | Gametes | Seminiferous tubules |
Mucus | Lubricant | Bulbourethral glands |
Water | Liquid medium | All accessory glands |
Buffers | Neutralise acidic vaginal environment | Prostate, bulbourethral glands |
Nutrients (fructose, citric acid, vitamin C, carnitine) | Nourish sperm | Seminal vesicles, prostate, epididymis |
Enzymes | Clot semen, then liquefy the clot | Seminal vesicles and prostate |
Zinc | Unknown; possible association with fertility | Unknown |
Prostaglandins | Smooth muscle contraction; may aid sperm transport | Seminal vesicles |
Semen characteristics:
Milky appearance
pH 7.4 (neutral to slightly alkaline, to buffer vaginal acidity)
Volume: approximately 1.5 mL per ejaculate
Normal sperm count: approximately 15 x 10⁶ per mL
Has a specific odour (spermine)
Clots after ejaculation, then liquefies (enzymatic process)
Erection:
A vascular event, not muscular
Under parasympathetic nervous system control (key point: parasympathetic, not sympathetic)
Also involves CNS and spinal integration
The penile blood vessels are the only vessels in the human body with dual parasympathetic and sympathetic innervation
Mechanism:
Stimuli (tactile via mechanoreceptors, erotic thoughts, visual) activate parasympathetic pathways
Pelvic neurons release nitric oxide (NO)
NO activates guanylyl cyclase, increasing cyclic GMP (cGMP)
cGMP causes smooth muscle relaxation in penile arterioles
Arterioles dilate, blood fills the corpora cavernosa and corpus spongiosum
Venous outflow is compressed, maintaining the erection
Important notes on erection:
Erection can occur without higher brain input (spinal reflex)
It can also be stimulated or inhibited by descending pathways from the cerebral cortex
Spontaneous erections occur during REM sleep
Ejaculation is a two-phase process:
1. Emission (sperm enters urethra):
Under sympathetic control
Rhythmic smooth muscle contraction of the epididymis and vas deferens pushes sperm forward
Accessory glands release their secretions
Internal urethral sphincter contracts to prevent retrograde ejaculation (semen flowing backwards into the bladder)
2. True ejaculatory phase (sperm exits urethra):
Under somatic (voluntary) motor control
Skeletal muscle contraction:
Ischiocavernosus muscle: stiffens the penis
Bulbospongiosus muscle: pushes semen forward to the external urethral opening
Defined as the inability to achieve or sustain a penile erection
Normal erection depends on NO production from endothelial cells and pelvic neurons
ED can result from impaired NO production (endothelial dysfunction)
Pharmacological treatment: PDE-5 inhibitors (sildenafil / Viagra)
PDE-5 normally degrades cGMP
Blocking PDE-5 increases cGMP levels, prolonging vasodilation and supporting erection
Requires some baseline NO production to work (does not create erection from nothing)
A controversial concept; not all men experience significant clinical effects
Affects approximately 50% of men over 50 years old
Characterised by declining testosterone levels
Despite lower testosterone, many men remain reproductively active
Spermatogenesis typically continues (unlike menopause in women, where oogenesis ceases entirely)
Lower testosterone levels may affect quality of life (energy, libido, mood, muscle mass) but the impact is variable
Precocious puberty (early onset):
Sexual maturation before age eight
May be caused by infection or tumour of the hypothalamus
a) True precocious puberty:
Normal pattern of HPG axis activation, just premature
Gametogenesis present
Causes: CNS lesions, hypothyroidism
b) Pseudoprecocious puberty:
Secondary sex characteristics appear, but no gametogenesis
Caused by abnormal exposure to androgens or oestrogens (exogenous or from a tumour)
Can occur in both sexes
Delayed puberty:
Females: no onset of menses by age 17
Males: no testicular development by age 20
Causes: hypogonadism, malnutrition, chronic disease, decreased responsiveness to sex hormones
No mathematical formulas. Key diagrams to review:
Cross-section of the seminiferous tubule showing Sertoli cells, germ cells at various stages, Leydig cells in the interstitium, and the blood-testis barrier
Spermatozoon structure: head (acrosome, nucleus), mid-piece (mitochondrial spiral), tail (flagellum)
Erection reflex pathway: stimulus to parasympathetic activation to NO release to cGMP to smooth muscle relaxation to vasodilation
Feedback diagram: GnRH to LH/FSH to Leydig/Sertoli cells, with testosterone and inhibin feeding back negatively
PDE-5 inhibitors (sildenafil, tadalafil) are among the most widely prescribed medications worldwide, and understanding the NO-cGMP-PDE-5 pathway is essential to knowing how they work and why they fail in patients with severe endothelial dysfunction. Varicocele repair is one of the most common surgical interventions for male infertility. Cryptorchidism correction (orchiopexy) is performed in infancy to preserve future fertility.
Students often think erection is under sympathetic control. It is not; it is primarily parasympathetic. A useful mnemonic: "Point" for parasympathetic (erection), "Shoot" for sympathetic (emission).
Many students believe Viagra "creates" an erection. It does not. It prevents the breakdown of cGMP, which means some baseline NO production (and therefore some degree of arousal) is still required.
A common error is confusing spermiogenesis (morphological differentiation, no cell division) with spermatocytogenesis (the mitotic and meiotic division phases).
Students sometimes state that andropause is equivalent to menopause. It is not. In andropause, testosterone declines gradually and spermatogenesis can continue; in menopause, oocyte reserves are depleted and ovarian function ceases.
⚠️ The three phases of spermatogenesis (spermatocytogenesis, spermiogenesis, spermiation) and what happens in each phase is a classic structured question.
⚠️ Sertoli cell functions are very frequently examined. Know the full list: support, BTB, ABP, inhibin, activin, luminal fluid, oestrogen, plasminogen activator.
⚠️ The blood-testis barrier and why it matters (autoimmune infertility if breached) is a favourite short-answer topic.
⚠️ Temperature control mechanisms (four mechanisms, plus pathologies like cryptorchidism and varicocele) are commonly tested.
⚠️ The NO-cGMP-PDE-5 pathway for erection is high yield. Be able to draw it and explain where Viagra acts.
⚠️ Know the difference between true and pseudo precocious puberty (presence or absence of gametogenesis).
⚠️ Emission versus ejaculation: different autonomic control (sympathetic versus somatic).
True or false: Spermatogenesis takes approximately 28 days to complete.
Fill in the blank: The blood-testis barrier is formed by _______ between adjacent _______ cells.
True or false: Erection is primarily under sympathetic nervous system control.
Fill in the blank: PDE-5 inhibitors work by preventing the breakdown of _______, which prolongs _______ of penile arterioles.
True or false: In andropause, spermatogenesis ceases entirely.
Answers: 1. False (approximately 65 to 70 days). 2. Tight junctions; Sertoli. 3. False (parasympathetic). 4. cGMP; vasodilation. 5. False (spermatogenesis typically continues despite declining testosterone).
Q: List the four mechanisms that maintain testicular temperature below core body temperature.
A: (1) Testes housed outside the body in the scrotum. (2) Scrotal sweat glands. (3) Pampiniform plexus acting as a countercurrent heat exchanger. (4) Tunica dartos and cremaster muscles adjusting testicular position.
Q: A patient presents with a varicocele. Explain why this may cause infertility.
A: A varicocele is an abnormal dilation of the pampiniform plexus veins. The pampiniform plexus normally cools arterial blood heading to the testis via countercurrent exchange. When dilated, this cooling mechanism is impaired, raising testicular temperature above the optimal range for spermatogenesis, which can reduce sperm count and quality.
Q: Describe the role of Sertoli cells in spermatogenesis. Name at least five specific functions.
A: Sertoli cells (1) physically surround and support developing germ cells, (2) form the blood-testis barrier via tight junctions, (3) produce androgen-binding protein (ABP) to maintain high local testosterone, (4) secrete inhibin (suppresses FSH) and activin (stimulates FSH), (5) produce luminal fluid that suspends released sperm, (6) produce plasminogen activator required for spermiation, and (7) create limited amounts of oestrogen via aromatase.
Q: Trace the pathway from sexual stimulus to penile erection, including the key molecular mediators.
A: A sexual stimulus (tactile or psychogenic) activates parasympathetic pathways via pelvic nerves. Parasympathetic neurons and endothelial cells release nitric oxide (NO). NO activates guanylyl cyclase in penile smooth muscle, increasing cyclic GMP (cGMP). cGMP causes relaxation of smooth muscle in penile arterioles, leading to vasodilation. Blood fills the corpora cavernosa and corpus spongiosum. Compression of venous outflow maintains the erection.
Q: Distinguish between true precocious puberty and pseudoprecocious puberty.
A: True precocious puberty involves premature but otherwise normal activation of the HPG axis. Both secondary sex characteristics and gametogenesis are present. Causes include CNS lesions and hypothyroidism. Pseudoprecocious puberty involves the appearance of secondary sex characteristics without gametogenesis, caused by abnormal exposure to sex hormones (from exogenous sources or hormone-secreting tumours) rather than HPG axis activation.
Q: Explain why retrograde ejaculation does not normally occur, and what mechanism prevents it.
A: During the emission phase of ejaculation, the internal urethral sphincter contracts under sympathetic control. This closes off the bladder neck, preventing semen from flowing backwards into the bladder. If this sphincter fails (due to nerve damage, surgery or certain medications), retrograde ejaculation results, where semen enters the bladder instead of exiting the urethra.
This material connects directly to the endocrinology block (HPG axis, steroid hormone synthesis, feedback loops) and to the clinical urology curriculum (infertility workup, erectile dysfunction management, testicular pathology). The blood-testis barrier and immune privilege concept also links to immunology. Understanding the autonomic control of erection and ejaculation connects to the broader autonomic nervous system module (parasympathetic versus sympathetic function).
male reproductive anatomy, testes, seminiferous tubules, Sertoli cells, Leydig cells, blood-testis barrier, spermatogenesis, spermatocytogenesis, spermiogenesis, spermiation, spermatozoa, acrosome, flagellum, epididymis, vas deferens, prostate gland, seminal vesicles, bulbourethral glands, Cowper's glands, pampiniform plexus, countercurrent heat exchange, cryptorchidism, varicocele, testicular temperature, androgen-binding protein, ABP, SSBG, testosterone, DHT, oestrogen, inhibin, activin, semen composition, fructose, prostaglandins, erection, ejaculation, emission, parasympathetic, nitric oxide, cGMP, PDE-5, sildenafil, Viagra, erectile dysfunction, impotence, andropause, precocious puberty, delayed puberty, pseudoprecocious puberty, hypogonadism, male infertility