Global warming and testis function: A challenging crosstalk in an equally challenging environmental scenario

The paper frames global warming as a progressive increase in environmental temperature with wide-ranging effects on ecosystems, economies, and human health. Within this context, male fertility and testicular function are highlighted as particularly vulnerable due to the testes’ anatomical position and dependence on precise thermoregulation. Although acute thermal shocks are known to impair spermatogenesis, quantifying the impact of real-world ambient temperature variation on human testis function is challenging due to human thermoregulation, heterogeneity in exposure models, and variable clinical outcomes. The review aims to synthesize physiological principles of body and testicular thermoregulation, summarize molecular and cellular effects of heat on testicular cells, and critically appraise epidemiologic evidence linking environmental temperature, semen quality, testosterone trends, and birth rates to assess whether climate warming contributes to declining male reproductive function.

- Evolution and thermoregulation of the human testis: Testes are externalized to maintain temperatures 2–4°C below core. Countercurrent heat exchange between the testicular artery and pampiniform plexus, scrotal vasodilation, sweating, and systemic reflexes (including increased respiratory rate upon scrotal warming) contribute to testicular thermoregulation. Varicocele impairs venous drainage and countercurrent exchange, increasing scrotal temperature (~1°C) and is improved by varicocelectomy. - Experimental heat stress models (animals): Acute scrotal/testicular hyperthermia in rodents (typically 42–43°C water-bath for 15–30 min) induces seminiferous degeneration, germ cell apoptosis, tight junction disruption (reduced occludin, claudin-3, ZO-1), meiotic failure, and altered expression of stress proteins. In mice, raising testicular temperature toward core levels (36–38°C) arrests spermatogenesis at defined stages. In bulls, modest scrotal heating (~32°C vs ~30°C for 96 h) increases lipid peroxidation and later DNA fragmentation with decreased motility and mitochondrial function. Heat stress also suppresses Leydig cell steroidogenesis (reduced T, downregulated StAR/CYP17) and may trigger compensatory gene expression changes. - Human exposures and occupational/lifestyle heat: Prolonged sitting/driving, laptop use near the groin, wet heat (hot baths/whirlpools), saunas, and varicocele elevate scrotal temperature and are associated with reversible decrements in semen quality; antioxidant capacity declines and DNA fragmentation/oxidative stress markers rise in heat-exposed groups (e.g., professional drivers, varicocele). Sauna exposure impaired sperm count and motility without altering circulating sex hormones in healthy men. - Seasonal and environmental epidemiology: Multiple large cohorts show sperm concentration, total count, and motility are inversely related to ambient temperature and temperature-humidity indices, with nadirs in summer/autumn and higher values in cooler seasons. An ambient temperature near ~13°C appears optimal for semen parameters, with decrements at temperatures above or below this point. Short-term temperature windows (30–60 days pre-collection) correlate with semen quality, aligning with spermatogenic timing. - Testosterone seasonality and secular trends: Seasonal T patterns are inconsistent across studies (peaks reported in winter, summer, or autumn). However, several population studies report an age-independent secular decline in serum testosterone across decades, even after adjusting for BMI and other covariates; most did not assess environmental temperature as a contributor. - Birth rate and temperature: Heat waves are associated with reduced birth rates 8–10 months later and a rebound at 11–13 months. A cross-national analysis (1860–1980) suggests higher maximum temperatures negatively affect total fertility rates, while greater annual temperature amplitudes may have positive associations, especially in settings with limited fertility interventions. - Mechanisms: Heat-induced oxidative stress (ROS overproduction), mitochondrial dysfunction, lipid peroxidation, DNA damage, cell cycle disruption, apoptosis, and tight junction perturbations are implicated in germ cell injury; Leydig cell steroidogenesis is heat-sensitive.

This is a narrative review. The authors synthesize physiological, experimental, clinical, and epidemiological literature regarding testicular thermoregulation and the effects of environmental and experimentally induced heat stress on spermatogenesis and steroidogenesis. Evidence spans: (1) comparative physiology and anatomy of testicular thermoregulation; (2) animal heat-stress models (rodents, rams, bulls) with controlled scrotal/testicular heating; (3) human observational and interventional heat exposures (occupational heat, lifestyle factors, saunas, wet heat, varicocele, device-related heating); (4) population studies relating ambient temperature and temperature variability to semen parameters; (5) studies on seasonal/secular trends in testosterone; and (6) demography linking temperature to birth rates. Detailed database search strategies and inclusion criteria are not specified.

- Testicular thermoregulation: - Human testes are maintained at ~2–4°C below core via countercurrent heat exchange (testicular artery ~37°C vs venous plexus ~35°C), scrotal vasodilation/sweating, and systemic reflexes (e.g., polypnea with scrotal warming in rams). - Varicocele impairs venous drainage and countercurrent efficiency, increasing scrotal temperature (~+1°C vs controls); microsurgical varicocelectomy improves thermoregulation. - Experimental heat stress and spermatogenesis: - Rodents exposed to 42–43°C scrotal/testicular heat (15–30 min) show rapid seminiferous degeneration, germ cell apoptosis, and meiotic failure; tight junction proteins (occludin, claudin-3, ZO-1) decrease within 24–48 h post-heat. - In mice, sustained testicular temperatures of 36–38°C arrest spermatogenesis at round spermatid (36°C), late spermatocyte (37°C), or primary spermatocyte (38°C) stages, indicating narrow thermal tolerance. - Bulls subjected to ~32°C scrotal temperature for 96 h display increased sperm lipid peroxidation (14 days), reduced mitochondrial membrane potential, motility, and membrane integrity, and elevated DNA fragmentation (28 days). - Human scrotal warming protocols (e.g., 43°C, 30 min/day for 10 days) lead to proteomic downregulation of reproduction-related proteins (e.g., AKAP4, ODF1, GAPDHS, SPESP1, ACTRT2) detectable weeks later. - Steroidogenesis under heat stress: - Animal studies consistently show reduced serum/intratesticular testosterone after scrotal/testicular heating, Leydig cell hyperplasia, and suppression of steroidogenic enzymes (e.g., StAR, CYP17); some studies show compensatory StAR upregulation later. - Human sauna exposure (80–90°C, 15 min twice weekly for 3 months) caused marked, reversible declines in sperm count/motility without significant changes in circulating sex hormones. - Mechanisms: - Heat triggers oxidative stress (ROS overproduction), mitochondrial dysfunction, lipid peroxidation, chromatin/DNA damage, tight-junction disruption, cell cycle arrest, apoptosis, and autophagy in testicular cells and sperm. - Environmental/seasonal epidemiology of semen: - Large cohorts (e.g., >4,000 to >10,000 men) show sperm concentration, total count, and motility inversely correlate with ambient temperature and THI; semen quality is generally higher in cooler seasons (winter/spring) and lower in warmer seasons (summer/autumn). - An ambient temperature around ~13°C is associated with optimal semen parameters; moving away from this (warmer or colder) reduces semen quality; temperature variability (day-to-day SD and max changes) also predicts lower sperm concentration months later. - Temperature effects are strongest for exposures in the preceding 30–60 days, aligning with spermatogenic timing; effects at 90 days are less consistent. - Testosterone trends: - Seasonal testosterone peaks vary across studies (winter/summer/autumn), with inconsistent circannual patterns. - Multiple population datasets report age-independent secular declines in serum testosterone across recent decades even after adjusting for BMI and other factors; most did not assess temperature as a covariate. - Birth rates and temperature: - Heat waves are followed by a reduction in birth rates 8–10 months later, with a rebound at 11–13 months; cross-country analyses suggest higher maximum temperatures are associated with lower total fertility rates, while greater annual temperature amplitudes may increase fertility in some contexts.

The synthesis supports that testicular function is highly temperature-sensitive: acute and modest scrotal/testicular heating disrupts spermatogenesis and, in many models, suppresses steroidogenesis via oxidative stress, tight junction disruption, meiotic failure, and germ cell apoptosis. Human studies of occupational/lifestyle heat exposure and controlled heat (sauna, wet heat) show reversible decrements in semen quality, consistent with animal findings. Epidemiologic data demonstrate that semen parameters vary seasonally and inversely with ambient temperature and temperature variability, with optimal performance near ~13°C. However, translating these findings to a causal link between progressive global warming and long-term declines in male reproductive function remains difficult. Confounding environmental changes (air pollution, nutrition/food systems, disease burden), evolving lifestyles, and limited precise individual heat exposure data (e.g., continuous scrotal temperature) complicate attribution. While heat waves can transiently reduce conception and birth rates, their timing and rebound effects, plus demographic and behavioral factors, obscure a direct male-factor pathway. For testosterone, secular declines are reported but temperature contributions are largely untested. Overall, acute and seasonal heat impacts are evident, but definitive evidence tying long-term climatic warming to declining semen quality and fertility is still insufficient.

Testicular function is intrinsically linked to temperature due to scrotal localization and specialized thermoregulation. A broad body of animal and human evidence shows that acute and subacute heat exposures impair spermatogenesis and often steroidogenesis through oxidative stress and related cellular pathways, with largely reversible effects. Population studies consistently reveal seasonal inverse associations between ambient temperature and semen parameters, with an apparent optimum near ~13°C, and heat waves are associated with short-term reductions in birth rates. Nonetheless, robust causal links between long-term global temperature rise and secular declines in semen quality, testosterone, and fertility remain unproven due to confounding environmental, behavioral, and methodological factors. Future research should prioritize: (1) precise characterization of individual heat exposures (including continuous scrotal temperature monitoring); (2) longitudinal studies linking temperature metrics (means, extremes, variability) with semen, hormonal outcomes, and reproductive endpoints; (3) mechanistic studies connecting ROS signaling to specific germ cell and Leydig cell pathways; and (4) integrated models accounting for co-exposures (air pollution), nutrition, and socioeconomic determinants.

- Lack of standardized exposure definitions and dose–response data for thermal stress in humans; ethical and logistical barriers to experimental human dosing. - Heterogeneity across animal models and human studies (exposure intensity/duration, endpoints), limiting direct comparability and translation. - Scarcity of precise, continuous scrotal temperature measurements in representative human cohorts. - Confounding by co-occurring environmental changes (air pollutants, nutrition/food security, disease burden) and lifestyle factors over decades, complicating attribution to temperature alone. - Limited long-term epidemiological data directly linking rising average temperatures to secular declines in semen quality, testosterone, and fertility outcomes. - Mechanistic gaps in connecting generalized oxidative stress to specific cell-type responses (e.g., germ cell apoptosis pathways, Leydig cell steroidogenesis) in vivo under realistic heat exposures. - Inconsistent findings on seasonal testosterone rhythms and lack of temperature covariates in secular testosterone trend studies.