The testicle, also known as the testis (plural: testes or testicles), is the male gonad in mammals, homologous to the female ovary.[1] It serves dual primary functions: the exocrine production of spermatozoa (sperm cells) through spermatogenesis and the endocrine secretion of androgens, chiefly testosterone, which regulates male secondary sexual characteristics, libido, and various physiological processes.[2][3]In adult human males, the paired testicles are ovoid structures, each typically measuring 3–5 cm in length, 2–3 cm in width, and 2–3 cm in depth, suspended within the scrotum—a skin and muscle sac that protects them and maintains an optimal temperature approximately 2–3°C below core body temperature to support spermatogenesis.[4] Internally, each testicle consists of seminiferous tubules where sperm production occurs, supported by Sertoli cells, and interstitial Leydig cells responsible for testosterone synthesis, all enclosed by a tough fibrous tunica albuginea.[2] The testicles develop embryonically from the genital ridge and descend from the posterior abdominal wall into the scrotum by birth, a process essential for fertility.[3] Disruptions in testicular function can lead to conditions such as infertility, hypogonadism, or testicular cancer, underscoring their critical role in male reproductive health.[5]
Anatomy in Humans
External Appearance
The testicle, also known as the testis, is a paired, ovoid reproductive organ typically measuring 4-5 cm in length, suspended within the scrotum.[2] It appears smooth and firm to the touch upon palpation through the scrotal skin, resembling the consistency of a hard-boiled egg without its shell.[6] The two testicles are positioned asymmetrically in the scrotum, with the left usually hanging slightly lower than the right, and each is anchored superiorly by the spermatic cord while the epididymis—a comma-shaped structure—attaches to its posterior surface.[2] The tunica vaginalis, a double-layered serous membrane, envelops the anterior and lateral aspects of the testicle, providing a slick, protective covering that contributes to its smooth external visibility and mobility within the scrotum.[2]In terms of age-related variations, testicles in youth present as smaller and smoother in appearance due to the underdeveloped scrotal skin, which lacks the rugose texture and pigmented bumps that develop during puberty and adulthood.[7] The scrotal skin's adaptations, such as its ability to contract and relax for thermoregulation, further influence the overall external presentation of the testicles.[8]
Size and Measurement
Human testicles are typically ovoid organs with average dimensions of 3-5 cm in length, 2-4 cm in transverse width, and 2-3 cm in anteroposterior depth.[9] The corresponding volume per testicle ranges from 12.5 to 25 mL in adults, reflecting individual variations influenced by genetics and health factors.[10][11]Clinical assessment of testicle size employs several standardized methods to ensure accuracy. The orchidometer, such as the Prader or Rochester type, involves comparing the testicle to a series of ellipsoid beads of known volumes for a quick estimation.[12] For more precise measurement, ultrasound is preferred, calculating volume using the ellipsoidformula: length × width × height × 0.52.[12] Manual techniques, including sliding calipers, allow direct dimensional assessment but are less reliable due to subjective placement.[12]Testicle size undergoes significant changes across the lifespan. In prepubertal boys, volumes are typically under 4 mL, marking minimal development prior to puberty onset.[13] Volumes peak during young adulthood, aligning with maximal reproductive function, before a gradual decline begins after age 50, with more pronounced reduction post-60 due to age-related tissue involution.[14]Testicle size serves as a key clinical indicator of reproductive health and fertility potential, as larger volumes generally correlate with higher sperm production and density in fertile men.[15] Reduced size may signal underlying gonadal function issues, prompting further evaluation without implying specific disorders.[15]
Internal Structure
The human testicle is internally organized into approximately 250 lobules, formed by fibrous septa that radiate from the mediastinum testis and extend inward from the tunica albuginea, dividing the organ into distinct compartments.[16] Each lobule houses one to four highly coiled seminiferous tubules, which constitute the primary structural units responsible for sperm production and occupy the majority of the testicular volume.[16] These tubules are suspended within a supportive framework of connective tissue that maintains the overall architecture and provides structural integrity.[17]The seminiferous tubules are tortuously coiled structures, each measuring up to 70 cm in length when uncoiled, with a diameter of approximately 150-250 micrometers.[18] At their posterior ends, the coils straighten into tubuli recti, which converge toward the mediastinum testis.[17] This central region contains the rete testis, an anastomosing network of channels that collects fluid and cellular contents from the tubules.[16]From the rete testis, 10 to 15 efferent ductules emerge, piercing the tunica albuginea to connect with the head of the epididymis, thereby forming the initial segment of the ductal pathway for sperm transport.[16] The spaces between the seminiferous tubules, known as the interstitial compartments, consist of loose connective tissue that houses clusters of Leydig cells.[19] This arrangement ensures efficient compartmentalization, with the connective tissue stroma providing both support and separation for the tubular and interstitial components.[16]
Cellular Composition
The human testicle consists primarily of seminiferous tubules, which account for 80-90% of the organ's volume, and an interstitium that comprises the remaining 10-20%.[20]The seminiferous tubules house two key cell types: Sertoli cells and germ cells. Sertoli cells are elongated, supportive cells that form the structural framework of the tubular epithelium and contribute to the blood-testis barrier through tight junctions between adjacent cells.[21] Germ cells, which constitute the majority of cells within the tubules, undergo developmental stages starting from spermatogonia at the basal layer, progressing to primary and secondary spermatocytes during meiosis, and maturing into round and elongating spermatids before becoming spermatozoa.[21]In the interstitium, Leydig cells serve as the primary endocrine cells, characterized by their polyhedral shape and location in clusters adjacent to capillaries; these cells occupy 10-20% of the testicular volume.[22] Peritubular myoid cells, thin and contractile, envelop the outer layer of the seminiferous tubules, enabling coordinated peristaltic movements that propel tubular fluid and support gamete transport.[21]
Vascular Supply and Layers
The arterial supply to the human testicle primarily originates from the paired testicular arteries, which arise directly from the anterolateral aspect of the abdominal aorta at the level of the second lumbar vertebra, just inferior to the renal arteries.[2] These arteries descend retroperitoneally, cross anterior to the ureters, and enter the inguinal canal within the spermatic cord to reach the testicle, where they anastomose with smaller contributions from the cremasteric artery (a branch of the inferior epigastric artery) and the artery to the ductus deferens (from the internal iliac artery via the inferior vesical artery).[23] Within the spermatic cord, the testicular artery is enveloped by the pampiniform venous plexus, forming a countercurrent system that aids in thermoregulation by cooling arterial blood through heat exchange with cooler venous blood (see Thermoregulation).[23]Venous drainage from the testicle occurs through the pampiniform plexus, a network of small veins surrounding the testicular artery and draining the testicle and epididymis.[2] These veins converge superiorly within the spermatic cord to form the testicular vein: the right testicular vein drains directly into the inferior vena cava at the L2 level, while the left testicular vein joins the left renal vein before entering the inferior vena cava.[23] This asymmetric drainage pattern contributes to the higher prevalence of left-sided varicoceles, which result from venous dilation due to incompetent valves or compression, but the normal pampiniform structure maintains efficient drainage and prevents such pathology under physiological conditions.[24]Lymphatic vessels from the testicle follow the course of the testicular arteries and veins through the spermatic cord, ultimately draining into the para-aortic (lumbar) lymph nodes at the level of the L2 vertebra.[23] This drainage pathway reflects the testicle's embryological origin from retroperitoneal tissues, bypassing inguinal nodes unlike scrotal skin lymphatics.[2]The testicle is enveloped by three principal connective tissue layers that provide structural support and protection. The outermost is the tunica vaginalis, a serous sac derived from the peritoneal processus vaginalis, consisting of visceral and parietal layers with a potential space containing a small amount of fluid to facilitate testicular movement and reduce friction.[24] Beneath this lies the tunica albuginea, a dense, white fibrous capsule composed of collagen and elastin fibers that encases the testicular parenchyma, forming incomplete septa that divide the interior into 200–300 lobules containing seminiferous tubules.[2] Internal to the tunica albuginea is the tunica vasculosa, a thin vascular layer of loose connective tissue interlaced with a plexus of capillaries and small blood vessels that nourishes the underlying seminiferous tubules.[24]Recent advances in microvascular imaging have enhanced varicocele diagnosis by assessing testicular perfusion and vascular integrity. Post-2020 studies utilizing color Doppler ultrasound demonstrate elevated resistance indices in testicular arteries of varicocele patients, indicating microvascular impairment and reduced perfusion as early diagnostic markers.[25] Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) further reveals altered perfusion patterns in infertile men with clinical varicoceles, providing quantitative insights into parenchymal damage.[26] Ultrasonic microvascular density mapping, a non-contrast technique, correlates low intratesticular microvascular flow with impaired spermatogenesis and predicts sperm retrieval success in obstructive cases, with thresholds like microvascular density >28.50/cm² indicating favorable outcomes.[27]
Blood-Testis Barrier
The blood-testis barrier (BTB) is a specialized structure formed by tight junctions between adjacent Sertoli cells within the seminiferous epithelium of the testis. These tight junctions divide the epithelium into two distinct compartments: the basal compartment, which contains vascular and lymphatic elements accessible to the systemic circulation, and the adluminal compartment, which houses developing spermatogenic cells.[28][29]Structurally, the BTB is a multilayered complex primarily composed of transmembrane proteins such as claudins (notably claudin-11) and occludins, which form the core of the tight junctions, along with associated adaptor proteins like zonula occludens (ZO-1, ZO-2). Claudin-11 and occludin interact to create a seal that restricts paracellular diffusion, while tricellulin contributes at tricellular contacts. This architecture is analogous to the blood-brain barrier, as both are among the tightest physiological barriers in mammals, providing selective permeability to maintain compartmentalized microenvironments.[28][29][30]The primary function of the BTB is to isolate post-meiotic haploid germ cells, which express novel autoantigenic proteins, from the immune system, thereby preventing autoimmune responses that could target these cells as foreign. This immunological protection is essential for spermatogenesis, as it sequesters developing sperm from immune surveillance in the basal compartment. The barrier's permeability is dynamically regulated by hormones, particularly androgens like testosterone, which stabilize tight junctions, and cytokines such as TGF-β, which facilitate germ cell transit through transient remodeling without compromising overall integrity.[28][29][31]Disruption of the BTB, such as through loss of key junctional proteins, compromises barrier integrity and is associated with infertility due to impaired spermatogenesis and increased germ cell apoptosis. For instance, silencing claudin-11 and occludin reduces tight junction function by up to 62%, leading to leakage and exposure of germ cells to immune factors.[30][32]Recent studies have highlighted age-related changes in BTB proteins; for example, in 2023 research on murine models, aging was shown to impair tight junction integrity via downregulation of occludin and claudins, exacerbated by inflammasome activation, contributing to declined spermatogenic function. Curcumin treatment in these models ameliorated such disruptions by restoring junctional proteins and reducing oxidative stress.[33][34]
Thermoregulation
The human testicle requires a temperature approximately 2-3°C below core body temperature, typically 34-35°C, to support optimal spermatogenesis.[35] This lower temperature is essential for the proper development and maturation of sperm cells, as elevated temperatures can impair germ cell proliferation and differentiation.[36]Several anatomical and physiological mechanisms maintain this temperature gradient. The scrotum facilitates heat dissipation through its thin, hairless skin and underlying dartos muscle, a layer of smooth muscle that contracts in response to cold, wrinkling the scrotal skin to reduce surface area and minimize heat loss.[37] The cremaster muscle, a striated muscle enveloping the spermatic cord, adjusts testicular position by elevating the testicles closer to the body during cold exposure to conserve warmth or lowering them away in warmer conditions to promote cooling.[38] Evaporative cooling occurs via sweat glands in the scrotal skin, which activate during heat exposure to release moisture and facilitate heat loss through evaporation.[39] Additionally, the pampiniform plexus of veins surrounding the testicular artery enables countercurrent heat exchange, where cooler venous blood from the testicle absorbs heat from incoming arterial blood, thereby cooling it before it reaches the testicular tissue.[40]Environmental changes trigger reflexive responses to fine-tune testicular temperature. The cremasteric reflex, elicited by stimuli such as cold or tactile input on the inner thigh, causes rapid contraction of the cremaster muscle to draw the testicle upward, protecting it from excessive cooling.[41] In contrast, heat prompts relaxation of both the cremaster and dartos muscles, increasing scrotal surface area and blood flow to enhance radiative and convective heat dissipation, while sweat gland activation further aids evaporative cooling.[42]Brief exposure to heat stress can adversely affect sperm function by reducing motility, as elevated temperatures disrupt mitochondrial activity and energy production in spermatozoa.[43] This underscores the importance of thermoregulatory mechanisms in preserving reproductive efficiency.
Development in Humans
Embryonic Formation
The embryonic formation of the testicle begins with the development of the gonadal ridge, a paired structure arising from the intermediate mesoderm along the urogenital ridge during the fourth to fifth weeks of gestation. This ridge forms as a thickening of the coelomic epithelium medial to the mesonephros, initially bipotential and capable of differentiating into either testes or ovaries depending on genetic signals.[3][44] By week 5, primordial germ cells (PGCs) originating from the yolk sac endoderm migrate through the dorsal mesentery of the hindgut to colonize the genital ridges, reaching them by approximately week 6 and integrating into the developing somatic structures.[45][46]In XY embryos, sex determination is triggered by the SRY gene on the Y chromosome (located at Yp11), which is expressed in the gonadal somatic cells around week 6 to 7 post-conception, initiating testis differentiation. The SRY protein acts as a transcription factor that upregulates SOX9, promoting the differentiation of Sertoli cells and suppressing ovarian pathways, thereby committing the bipotential gonad to a testicular fate.[3][45] Without SRY expression, as seen in XX embryos, the gonad defaults toward ovarian development. Recent studies using mouse models with SRY knockouts or transgenes have confirmed SRY's critical role, demonstrating that its absence leads to ovarian differentiation in XY gonads, while targeted overexpression can induce testis formation even in the absence of a functional Y chromosome.[47][48]As differentiation proceeds by week 7 to 8, the medullary cords—solid clusters of epithelial cells including pre-Sertoli cells and PGCs—form within the gonadal ridge under SRY influence, elongating and anastomosing to establish the foundational architecture of the testis. These medullary cords eventually canalize during later development to form the seminiferous tubules, the sites of future spermatogenesis, while interstitial spaces give rise to Leydig cells that begin testosterone production around week 8.[45][44] Single-cell analyses of human fetal gonads have revealed that by 6-7 post-conception weeks, SRY-positive Sertoli precursors organize PGCs into cord-like structures, marking the transition from bipotential to distinctly testicular organization.[46]
Descent and Pubertal Maturation
During fetal development, the testes originate in the abdominal cavity near the kidneys and undergo a process of descent into the scrotum to ensure proper thermoregulation for future spermatogenesis. This descent primarily occurs in the inguinoscrotal phase between weeks 25 and 35 of gestation, during which the testes migrate from the abdomen through the inguinal canal into the scrotum.[3] The gubernaculum, a gelatinous cord-like structure connecting the testis to the scrotum, plays a crucial guiding role by swelling and elongating under the influence of hormones such as insulin-like hormone 3 (INSL3) and androgens, facilitating the processus vaginalis formation and pulling the testis along its path.[49] Incomplete descent, known as cryptorchidism, affects approximately 3% of full-term male newborns, with the majority of cases being unilateral (right side more common than left).[50] While many cryptorchid testes descend spontaneously within the first few months postnatally, persistent cases increase risks for infertility and testicular cancer.[50]Recent research highlights the role of environmental factors in disrupting this descent process. Maternal exposure to endocrine-disrupting chemicals (EDCs), such as phthalates and bisphenol A, during pregnancy has been linked to elevated rates of cryptorchidism by interfering with INSL3 signaling and androgen action in the gubernaculum.[51] A 2024 review emphasizes that these ubiquitous pollutants, found in plastics and personal care products, contribute to adverse male reproductive outcomes, including incomplete testicular descent, underscoring the need for reduced exposure during critical gestational windows.[52]Pubertal maturation of the testes begins around ages 9-14 years and is triggered by a surge in gonadotropin-releasing hormone (GnRH) from the hypothalamus, leading to increased pulsatile secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland.[53] LH stimulates Leydig cells to produce testosterone, which supports spermatogenesis and secondary sexual characteristics, while FSH promotes Sertoli cell proliferation to nurture developing germ cells.[53] The first sign of puberty is testicular enlargement at Tanner stage 2, where volume increases from prepubertal levels of 1-3 mL to approximately 4 mL per testis, reaching approximately 9-15 mL per testis by mid-puberty (Tanner stage 3) due to seminiferous tubule expansion.[54]Spermatogenesis initiates during this stage, with early sperm production (spermarche) typically occurring around age 13-14 years, marking the transition to reproductive capability.[55]
Physiology
Spermatogenesis
Spermatogenesis is the process by which diploid germ cells in the seminiferous tubules of the human testicle develop into mature haploid spermatozoa, occurring continuously from puberty onward. This complex differentiation begins with spermatogonial stem cells, which undergo mitotic divisions to maintain the stem cell pool and produce committed progenitors. Type A spermatogonia differentiate into type B spermatogonia, which then enter meiosis as primary spermatocytes. The entire process spans approximately 64-74 days, with the seminiferous epithelium cycling through defined stages every 16 days to ensure synchronized progression.[56][57]The meiotic phase commences with primary spermatocytes (4n DNA content) undergoing meiosis I, involving homologous chromosome pairing and recombination during prophase I substages (leptotene, zygotene, pachytene, and diplotene), resulting in haploid secondary spermatocytes (2n DNA). Meiosis II rapidly follows without DNA replication, yielding four round spermatids (1n DNA) from each primary spermatocyte. Spermatids then undergo spermiogenesis, a post-meiotic transformation that includes nuclear condensation, acrosome formation, flagellum development, and cytoplasmic reduction to produce streamlined spermatozoa capable of motility and fertilization. This maturation occurs within the adluminal compartment of the seminiferous tubules, supported by the structural framework of the epithelium.[56][58]Spermatogenesis is tightly regulated by hormonal signals, primarily follicle-stimulating hormone (FSH) and testosterone, which act indirectly through Sertoli cells to nurture germ cell development. FSH binds to receptors on Sertoli cells, promoting their proliferation and secretion of nutrients and signaling molecules essential for spermatogonial survival and initiation of meiosis, while also enhancing Sertoli-germ cell adhesion. Testosterone, secreted by Leydig cells in response to luteinizing hormone, maintains high intratesticular concentrations (25-125 times serum levels) and is indispensable for meiotic progression and spermiogenesis; it prevents germ cellapoptosis and regulates stage-specific events like spermiation via androgen receptor signaling in Sertoli cells, peaking at cycle stage VII.[59][60]In humans, each testicle produces 100-200 million spermatozoa daily, ensuring a robust supply for reproduction despite high attrition rates, with only about 25% of initiated germ cells reaching maturity. The microenvironment within the seminiferous tubules is critical, featuring intimate Sertoli-germ cell interactions that provide structural support, nutrient transport, and paracrine signaling tailored to each developmental stage. Recent single-cell RNA sequencing studies from 2022 have elucidated these dynamics, identifying distinct transcriptional trajectories across germ cell subtypes—such as State 0 spermatogonial stem cells—and revealing key ligand-receptor interactions, like those involving GDNF and KIT, that govern niche signaling and stage-specific maturation between Sertoli and germ cells.[58][61][62]
Endocrine Functions
The testicles serve as key endocrine organs in males, primarily through the production of hormones that regulate reproductive and secondary sexual characteristics. Leydig cells, located in the interstitial tissue of the testes, are responsible for synthesizing and secreting testosterone, which accounts for approximately 95% of the circulating androgens in the male body.[63] This production is stimulated by luteinizing hormone (LH) from the anterior pituitary, with peak daily output reaching about 7 mg in healthy adult males.[64]In addition to testosterone, Sertoli cells within the seminiferous tubules produce inhibin and activin, peptide hormones that play crucial roles in modulating gonadotropin secretion. Inhibin, particularly inhibin B, exerts negative feedback on follicle-stimulating hormone (FSH) release from the pituitary, helping to fine-tune gonadal function and prevent overstimulation.[65] Conversely, activin promotes FSH secretion, maintaining a dynamic balance that supports overall endocrine homeostasis in the reproductive axis.[66]These hormonal outputs are integrated into the hypothalamic-pituitary-gonadal (HPG) axis, a feedback loop that ensures coordinated regulation of testicular endocrine activity. The hypothalamus releases gonadotropin-releasing hormone (GnRH) in pulses, stimulating the pituitary to secrete LH and FSH; in turn, testicular hormones like testosterone and inhibin provide negative feedback to suppress GnRH and gonadotropin release, preventing excessive stimulation.[67] This axis maintains stable hormone levels essential for male physiology.Testosterone exerts widespread systemic effects, including promotion of muscle protein synthesis and growth, which contributes to increased lean body mass and physical strength, as well as enhancement of libido and sexual motivation.[68] Low testosterone levels are associated with reduced muscle mass and diminished sexual desire, underscoring its anabolic and behavioral roles.[69]Research as of 2025 has explored selective estrogen receptor modulators and aromatase inhibitors in the treatment of functional male hypogonadism related to obesity and aging, with systematic reviews indicating potential benefits in normalizing testosterone levels.[70]
Genetic Expression
The genetic expression in the human testicle is characterized by a unique repertoire of genes and proteins that support spermatogenesis, hormoneregulation, and cellular maintenance. The SRY gene, located on the Y chromosome, plays a pivotal role in initiating testis differentiation by activating downstream pathways that promote male gonadal development.[71] In mature testes, DMRT1 maintains Sertoli cell identity and supports ongoing germ cell differentiation through transcriptional regulation.[72] Similarly, USP9Y, another Y-linked gene, is essential for spermatogenesis, where its ubiquitin-specific protease activity regulates protein turnover in germ cells to ensure proper meiotic progression.[73]Protein expression profiles in the testicle exhibit compartment-specific patterns that align with functional zones. High levels of protamines, particularly protamine 1 and 2, are expressed in elongating spermatids and mature sperm, where they replace histones to compact chromatin and protect genetic material during fertilization.[74] Androgen receptors (AR) are prominently expressed in Leydig cells, facilitating testosterone synthesis in response to luteinizing hormone, and in Sertoli cells, where they mediate paracrine signaling to support germ cell maturation.[75] These proteins show spatial heterogeneity: genes involved in early spermatogonial proliferation, such as those for cell cycle regulators, predominate in the basal compartment beneath the blood-testis barrier, while adluminal compartment expression favors meiosis- and spermiogenesis-associated transcripts, including those for acrosome formation and flagellar assembly.[76]Recent proteomic studies have illuminated age-related shifts in testicular gene and protein expression. A 2023 analysis of the testis-specific proteome revealed progressive downregulation of proteins linked to energy metabolism and oxidative stress response in aging Leydig and Sertoli cells, correlating with declining testosterone production and spermatogenic efficiency.[77] As of 2025, single-cell transcriptomic atlases of the human testis have further revealed two waves of molecular and cellular changes during aging, including responses in testicular progenitor cells and uneven spatial distributions of senescence signatures across compartments.[21]
Clinical Aspects
Injuries and Protective Measures
Testicular injuries primarily result from blunt or penetrating trauma to the scrotum. Blunt trauma, often occurring during sports, motor vehicle accidents, or falls, involves compressive forces that can cause contusions or ruptures of the testicular tunica albuginea.[78][79] Penetrating injuries, typically from stab wounds or gunshots, directly lacerate testicular tissue and are associated with higher severity due to unpredictable damage paths.[80][78]Common symptoms of testicular trauma include acute scrotal pain, swelling, bruising, and hematoma formation, which may extend to the scrotal skin or abdominal wall.[81][82] Additional signs can involve nausea, vomiting, hematuria, or fever if infection develops.[81][82] The scrotal layers, including the tunica vaginalis and dartos fascia, offer limited natural cushioning against such impacts.[78]Complications from testicular trauma include rupture, which occurs in approximately 50% of direct blunt scrotal injuries, leading to extrusion of seminiferous tubules and potential ischemia if untreated.[79] Hematomas and infections are also frequent, while trauma can rarely precipitate testicular torsion by disrupting vascular attachments.[79][78]Protective measures emphasize preventive gear and prompt intervention. Athletic supporters or cups, worn during contact sports, reduce blunt trauma risk by immobilizing the testes and absorbing impacts.[83][81] Athletic cups constructed from impact-resistant materials such as polycarbonate can disperse forces more effectively than traditional designs.[78] The American Urological Association recommends early surgical exploration for suspected rupture, involving debridement, tunica repair, and orchiopexy to secure the testis and prevent recurrent torsion.[78] General prevention guidelines from urological societies advocate seatbelt use in vehicles and avoidance of high-risk activities without protection.[81]
Diseases and Pathologies
Testicular cancer primarily consists of germ cell tumors, which account for the vast majority of cases and represent approximately 1% of all cancers in men.[84] These tumors most commonly affect young men aged 15 to 35, with risk factors including cryptorchidism (undescended testis), which increases the relative risk by 3.7 to 7.5 times compared to the general population.[85] Symptoms often include a painless lump or swelling in the testicle, along with possible heaviness or aching in the scrotum.[86]Infections of the testicle, such as orchitis and epididymitis, are significant causes of acute scrotal pathology. Orchitis, frequently associated with mumps virus infection in unvaccinated individuals, typically presents with unilateral testicular pain, swelling, fever, and constitutional symptoms like headache and malaise.[87]Mumps orchitis occurs in about 20-30% of post-pubertal males with mumps parotitis and can lead to testicular atrophy in severe cases.[88]Epididymitis, often bacterial in origin (e.g., from sexually transmitted infections like chlamydia or gonorrhea in younger men, or enteric organisms in older men), manifests as gradual onset of scrotal pain, swelling, dysuria, and urethral discharge.[89]Testicular torsion involves the twisting of the spermatic cord, leading to vascular compromise and ischemia of the testis, constituting a urological surgical emergency.[90] It predominantly affects adolescents and young adults, with symptoms including sudden, severe unilateral scrotal pain, nausea, vomiting, and swelling; the testicle may appear high-riding or horizontally oriented on examination.[91] Prompt surgical intervention within 6 hours of symptom onset is critical to salvage the testis, as prolonged torsion results in irreversible damage.[92]Varicocele, characterized by dilation of the pampiniform plexus veins in the scrotum, has a prevalence of about 15% in the general male population but rises to 35-40% among men with infertility.[93] It is often asymptomatic but can cause a dull ache or heaviness, worsened by standing; fertility impacts include impaired semen parameters such as reduced sperm count, motility, and increased DNA fragmentation due to oxidative stress and elevated scrotal temperature.[94] Recent genetic research highlights hereditary components, with varicoceles occurring at higher rates in first-degree relatives and associations with specific genetic variants influencing venous valve function.[95]
Hormonal Interventions and Effects
Hormonal interventions involving anabolic-androgenic steroids (AAS) profoundly disrupt testicular function through negative feedback on the hypothalamic-pituitary-gonadal axis, suppressing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, which in turn reduces endogenous testosterone production by Leydig cells and impairs spermatogenesis.[96] This suppression commonly leads to testicular atrophy, with chronic AAS users experiencing significant shrinkage of the testes due to diminished germ cell proliferation and Sertoli cell support.[97] To counteract this atrophy, many AAS users concurrently administer human chorionic gonadotropin (hCG), which mimics LH to stimulate Leydig cell activity and partially preserve testicular volume, though full recovery of size and function may take years after cessation and is often incomplete.[98]In contrast, hCG serves as a therapeutic agent in hormone replacement for hypogonadotropic hypogonadism, where it directly stimulates the testes to restore endocrine and exocrine functions. By binding to LH receptors on Leydig cells, hCG promotes testosterone synthesis and supports spermatogenesis, often leading to improved fertility outcomes in affected men when administered at doses such as 1500 IU twice weekly, adjusted based on serum testosterone levels.[99] Clinical studies demonstrate that hCG monotherapy effectively alleviates hypogonadal symptoms, including low libido and fatigue, while maintaining or re-establishing spermatogenic capacity without the need for concurrent testosterone replacement, making it a preferred option for patients desiring fertility preservation.[100]Chemotherapy and radiation therapies for cancer frequently induce damage to spermatogonial stem cells in the testes, resulting in transient or permanent azoospermia and oligospermia due to direct cytotoxicity and DNA strand breaks in germ cells. Spermatogonia, the most radiosensitive testicular cells, sustain injury from radiation doses as low as 0.1 Gy, with higher exposures (e.g., 2-3 Gy) affecting spermatocytes and leading to prolonged infertility; chemotherapy agents like alkylating drugs exacerbate this by depleting germ cell pools within 2-3 months of treatment.[101] To mitigate these effects, fertility preservation strategies such as sperm banking are recommended prior to therapy, allowing future assisted reproductive techniques, though recovery of spermatogenesis occurs in fewer than 30% of cases post-high-dose conditioning regimens, with lower radiation doses correlating to higher restoration rates over 12 weeks to years.[102]Emerging research on glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide and liraglutide used off-label for weight management in overweight or obese men, indicates potential enhancements in testicular function without adverse impacts. These agents have been associated with increased serum testosterone levels and improved sperm motility and count in clinical trials, likely through weight loss-mediated reductions in inflammation and metabolic stress on Leydig and Sertoli cells.[103] In vitro and animal models further suggest no detrimental effects on sperm quality or proliferation, with semaglutide demonstrating protective roles against oxidative damage in diabetic testicular dysfunction, highlighting their promise as adjuncts in metabolic disorders affecting reproduction.[104]
Society and Culture
Etymology and Terminology
The word testis, the Latin term for the male reproductive gland, derives from the Proto-Indo-European root tri-, meaning "three," reflecting its original sense as a "witness" or impartial third party in legal contexts.[105][106] The English testicle, first recorded in the early 15th century, is a diminutive form from Latin testiculus, literally "little witness," emphasizing the paired structure of the glands.[107]In Greek, the equivalent term is orchis (ὄρχις), meaning "testicle," derived from the Proto-Indo-European h₁órǵʰis, also denoting the organ, due to its shape resembling tubers or bulbs.[108] This root influenced botanical nomenclature, as the orchid flower's tubers mimic testicles, but in medicine, it forms prefixes like orchido- or orchio-, used in terms such as orchidopexy (surgical fixation of the testicle) to denote testicular structures or conditions.[109][110] The distinction between testis (preferred in scientific Latin) and testicle (common in English anatomy) arose in the 17th century with the adoption of classical terms in medical texts, though both remain interchangeable in modern usage.[111]Vulgar terms for the testicles have long contrasted with anatomical ones, with "balls" emerging in the early 14th century as slang from [Old English](/page/Old English) beall, referring to spherical objects and applied to the glands' rounded shape.[112] This usage persisted through Middle English, evolving into phrases like "bollocks" (from [Old English](/page/Old English) bealluc, "testicle"), which by the 19th century carried both literal and exclamatory senses of nonsense. Modern variations include "nuts" (from the 17th century, likening sperm to seeds) and "eggs" (due to oval form), often used in informal or humorous contexts across English dialects.[113][114]During the 19th century, Victorian sensibilities prompted a surge in euphemisms in literature and polite discourse, reflecting broader cultural taboos around sexuality; terms like "thingumbobs" or "bawbels" appeared in slang dictionaries to obliquely reference the testicles, avoiding direct vulgarity in print.[115][116] These shifts paralleled increased censorship in British and American publications, where anatomical discussions in medical journals retained Latin terms while novels employed circumlocutions like "vitals" or "privates" to maintain decorum.[117]
Cultural and Symbolic Roles
In ancient Egyptian culture, testicles held profound symbolic significance as emblems of fertility and virility, often depicted in religious iconography alongside the god Min, who was portrayed in ithyphallic form to represent sexual potency and agricultural abundance. Amulets and artifacts featuring exaggerated male genitalia, including the testicles, were employed as protective talismans against infertility and ailments of the reproductive system, underscoring their role in rituals invoking divine favor for procreation.[118][119] Similarly, in ancient Greece, testicles appeared in oversized forms in art and mythology, linked to deities like Priapus and Hermes, where they symbolized generative power, good fortune, and apotropaic protection against evil. Ithyphallic statues and herms, common in public spaces, emphasized the testicles' association with sexuality and communal well-being, reflecting beliefs in their role in producing male and female offspring respectively from the right and left sides.[120][121]In modern media, testicles often serve as a source of humor, particularly through depictions of groin trauma in comedy films and stand-up routines, which exploit their physical vulnerability to elicit laughs and underscore male fragility. This trope, prevalent in slapstick scenarios across cinema, transforms a site of potential pain into a relatable punchline, as seen in sequences where characters endure kicks or mishaps to the area for comedic effect.[122] However, such portrayals coexist with taboos, leading to censorship in artistic representations; historical examples include the Renaissance addition of fig leaves to cover genitalia on classical sculptures, a practice rooted in Christian moral standards that persisted into modern exhibitions where exposed testicles provoke controversy and demands for concealment.[123][124] These tensions highlight ongoing societal discomfort with male nudity, contrasting ancient reverence with contemporary prudery.Ritual practices involving testicles have historically included castration, the surgical removal of the testes to produce eunuchs, who occupied roles of trusted service in courts and temples across empires like the Ottoman, Byzantine, and Chinese, symbolizing emasculation as a means of ensuring loyalty and suppressing sexual agency. Such procedures, often performed in adolescence, were embedded in religious and political ceremonies, as with the cult of Cybele where self-castration honored the goddess and conferred spiritual status.[125][126] In sports culture, testicles inspire metaphors of bravery and endurance, with idioms like "grow a pair" or "testicular fortitude" evoking resilience and competitive affiliation, where the organs represent the willingness to endure risk and rivalry on the field.[127]Gender studies frame testicles as pivotal to masculinity's construction, embodying both potency and precariousness, often invoked in cultural exhortations to "grow a pair" that reinforce normative male toughness while exposing underlying anxieties about vulnerability. Scholars argue for greater attention to the testicles in men's studies, moving beyond phallocentric analyses to explore their relational and embodied dimensions.[128]Queer theory further disrupts these associations, complicating binary masculinity by examining how testicular symbolism intersects with non-normative identities, challenging heteronormative potency and advocating for fluid, inclusive interpretations of bodily agency in contemporary discourse.[128][129]
Comparative Anatomy
External Features Across Species
In mammals, external testicles often appear pendulous within a scrotal sac, facilitating thermoregulation, though significant variations exist across species. For instance, in elephants (Elephas maximus and Loxodonta africana), the testicles are permanently internal, positioned near the kidneys in the abdominal cavity rather than descending into a scrotum, which protects them from external temperatures while maintaining functionality at core body heat.[130] Similarly, in phocid seals such as the southern elephant seal (Mirounga leonina), testicles are located para-abdominally under thick layers of insulating blubber (7-8 cm), remaining internal and non-scrotal to prevent heat loss during prolonged dives in cold waters, with cooling achieved via vascular countercurrent exchange from hind flippers.[131] These adaptations contrast with scrotal species like otariid seals, highlighting how aquatic lifestyles influence external visibility and positioning.Birds exhibit no external testicles, as their gonads are entirely internal and retained within the abdominal cavity near the kidneys, a condition retained from reptilian ancestors to streamline body form for flight.[132]Avian testes are typically ovoid or elongated, varying in size seasonally but always concealed, with asymmetry often observed where the left testis is larger.[133]Reptiles display diverse external features in their testicles, which are generally internal but show structural variations; for example, in fossorial blind snakes of the genera Typhlops and Leptotyphlops, the testes are multilobed, compact, and abdominal, adapting to burrowing lifestyles by reducing protrusion.[134] In other reptiles like lizards and snakes, testicles remain non-pendulous and hidden, though associated structures such as hemipenes may influence visible genital morphology during mating.In fish, which possess testicular analogs rather than true testicles, external features include seasonal swelling of the gonads during reproductive cycles; for instance, in teleosts like the freshwater fish Channa gachua, testes thin during non-breeding months but swell noticeably from June to August to support spawning.[135] This cyclical enlargement, driven by hormonal surges, enhances visibility or palpability externally in some species, aiding mate attraction or release of milt.Evolutionarily, the external positioning of testicles in many endothermic mammals arose to cool spermatogenesis below core body temperature (approximately 2-3°C lower), preventing DNA damage in sperm; this trait likely emerged in early mammals around the Jurassic, as internal retention in basal lineages like monotremes and elephants underscores an ancestral state modified for thermoregulation in warm-blooded species.[136]
Positional Variations
In various animal species, the position of the testicles exhibits significant diversity, ranging from fully internal placements to external or transitional configurations, reflecting evolutionary adaptations to environmental pressures and physiological needs. Internal testicles are retained in several taxa, while external positioning predominates in most mammals, with some featuring mechanisms for retraction.In cetaceans such as whales and dolphins, the testicles remain located within the abdominal cavity near the kidneys, rather than descending into a scrotum.[137] This internal positioning contributes to hydrodynamic streamlining by eliminating external protrusions that could increase water resistance during swimming, and it also minimizes heat loss in aquatic environments through associated vascular countercurrent heat exchange systems that maintain optimal temperatures for spermatogenesis despite the body's core warmth.[138] Similarly, in birds, the testicles are fixed internally, positioned dorsally within the coelom adjacent to and cranial to the kidneys, without descent into an external sac. This arrangement is feasible because avianspermatogenesis is adapted to function effectively at the higher core body temperatures (often 40–42°C) characteristic of birds, obviating the need for external cooling mechanisms observed in many mammals.[139]Among mammals, the testicles of most species descend into an external scrotum during development, positioning them outside the abdominal cavity to facilitate thermoregulation by maintaining a temperature gradient approximately 2–4°C below core body temperature, essential for sperm production.[139] In rodents, however, this external position is complemented by a highly contractile cremaster muscle that enables retraction of the testicles into the abdominal cavity when needed, such as during cold exposure or stress, thereby providing dynamic protection and temperature control.[140]Monotremes, the most basal mammalian lineage, represent a transitional state in testicular positioning; for instance, in the platypus, the testicles do not fully descend but remain intra-abdominal throughout life, lacking a scrotum and exhibiting only partial or temporary migration toward the inguinal region during reproductive seasons, akin to an evolutionary intermediate between reptilian internal retention and therian descent.[141]These positional variations are driven by adaptive pressures, including protection from physical trauma in predatory species—where internal or retractable configurations reduce vulnerability during high-risk activities like hunting—and thermoregulation in herbivores, where external scrotal placement allows efficient cooling to support fertility in warm climates or during exertion, preventing heat-induced sperm damage.[139]
Size and Structural Adaptations
Testicle size varies significantly across animal species, often reflecting evolutionary pressures such as sperm competition and mating systems. In primates, relative testes mass is notably large, particularly in species with promiscuous mating where females copulate with multiple males, promoting intense sperm competition that favors increased sperm production.[142] For instance, chimpanzees exhibit testes comprising up to 0.3% of body mass, compared to much smaller proportions in monogamous primates like gorillas.[143] Conversely, species with internal testes, such as many fish and some mammals like elephants, tend to have the smallest relative testes size, as abdominal positioning reduces the need for large external structures and aligns with lower sperm competition levels.[144]Internally, the structure of testicular tissue shows marked differences between vertebrates. In fish, spermatogenesis occurs in simplified, cystic arrangements without true seminiferous tubules; instead, germ cells develop within enclosed cysts formed by Sertoli cells, leading to a more compact organization.[145] Mammals, by contrast, feature highly complex, coiled seminiferous tubules where spermatogenesis proceeds in a continuous wave, supported by elongated Sertoli cells that span the tubule wall.[146] Leydig cells, responsible for testosterone production, also vary across species: in mammals, they are typically clustered in the interstitial tissue with distinct fetal and adult forms differing in origin and function, while in fish, analogous interstitial cells are more diffusely distributed and adapted for seasonal steroidogenesis.[147][148]Structural adaptations often respond to reproductive cycles. In deer species like the fallow deer (Dama dama), testes undergo seasonal enlargement, with volume peaking just before the rutting season in autumn—reaching up to double the non-breeding size—driven by photoperiodic cues to maximize sperm output during brief breeding windows.[149] Humans, however, exhibit aseasonal testicular function, maintaining consistent size year-round without such fluctuations.[144] These adaptations tie into evolutionary allometry, where testes mass scales positively with body size across mammals (allometric exponent ≈1.3), but deviations occur based on ecological factors like mating strategy.[150]Recent genomic studies have begun identifying genetic bases for these size variations. A 2024 analysis in piglets revealed candidate genes like SOX9 influencing early testicular development and size through regulation of cell proliferation in seminiferous structures.[151] Cross-species transcriptomic comparisons from the same year highlighted conserved genes that drive the molecular evolution and genetic basis of male infertility among species.[152]