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

Global warming, the continuous increase in Earth's average temperature since the Industrial Revolution, is a significant concern with far-reaching consequences across various sectors, including human health. A major area of concern is the potential impact of rising temperatures on male fertility and testis function. The testis, with its unique developmental process, anatomical characteristics (external location in the scrotum), and dependence on a central endocrine axis, is particularly susceptible to environmental changes. Exposure to thermal shock is known to negatively affect spermatogenesis, a critical testicular function. However, the extent to which environmental temperature variations impact testis function in homeothermic mammals like humans, who have thermoregulatory capabilities, is not fully understood. This review aims to comprehensively evaluate the influence of environmental temperature on testicular function, spanning physiological concepts of body and testis thermoregulation, molecular mechanisms, and the evidence from epidemiological studies. The lack of consistency in study models and the challenges of defining exposure levels and clinical outcomes add to the complexities.

The review draws upon a substantial body of literature exploring the relationship between temperature and male fertility. Studies highlighting the global decline in fertility rates and the secular trend of decreasing semen quality are discussed, particularly focusing on sperm concentration and total sperm count. The review also explores the methodological biases in studying the impact of temperature on fertility, highlighting the need for toxicological approaches to establish precise thermal fertility limits. The challenges in directly measuring offspring production in some species, leading to reliance on biomarkers such as semen parameters, are also addressed. The limitations of relying solely on animal models and the difficulty in translating findings to humans are acknowledged.

This review integrates information from various sources including existing literature on human physiology and thermoregulation. The authors provide a detailed examination of testicular thermoregulation mechanisms, emphasizing the countercurrent heat exchange system between the testicular artery and the pampiniform venous plexus. They explore the role of scrotal vasodilation and sweating, and the systemic reflex reactions involved in maintaining optimal testicular temperature. Animal models of heat stress are reviewed, analyzing the effects on spermatogenesis and steroidogenesis across different mammalian species, including rodents, bulls, and rams. The methodology sections describe the various heat stress models used, including scrotal insulation, water baths, and scrotal bags. The molecular mechanisms involved are analyzed, focusing on the role of oxidative stress, apoptosis, and the dysregulation of specific proteins. In the human studies, this review includes studies examining occupational exposure to heat, the impact of lifestyle factors such as prolonged sitting, the use of saunas and hot baths, and the correlation between environmental temperature and semen quality. Specific studies are analyzed, focusing on the design, methodologies used, strengths, and limitations of each. This review uses data obtained from large datasets and epidemiological studies that correlated environmental temperature (including seasonal variations and heat waves), air pollutants, and other environmental factors with human semen parameters, testosterone levels, and birth rates. The analysis involves exploring seasonal variations in semen parameters and testosterone levels in different populations, acknowledging the role of confounding variables.

The review reveals a strong correlation between increased environmental temperature and adverse effects on testicular function. Acute heat stress in animal models consistently leads to impaired spermatogenesis and steroidogenesis, primarily through mechanisms involving oxidative stress, cell cycle disruption, and germ cell apoptosis. Studies in humans consistently demonstrate that increased scrotal temperature, whether from occupational exposure, lifestyle factors, or environmental conditions, is linked to reduced sperm quality (concentration, motility, morphology) and lower testosterone levels. Epidemiological studies show a seasonal trend in semen parameters, with lower values observed during warmer months. Some studies suggest a negative correlation between extreme environmental temperatures and birth rates. While several studies demonstrate an age-independent decline in serum testosterone levels over time, the specific role of environmental temperature in this decline requires further investigation. Studies on seasonal variations of sperm parameters demonstrate a highly significant, inverse correlation with environmental temperatures, with an optimal temperature of 13°C for best spermatogenic performance. A decline in sperm parameters is observed with increasing distance from this optimum and a sharp drop at extreme temperatures. Birth rates also display a seasonal trend, seemingly affected by extreme temperatures. However, connecting the rising trend of ambient temperature with the decline in sperm parameters and global birth rates remains challenging.

The findings of this review demonstrate a clear association between environmental temperature and male reproductive health, though establishing direct causality remains complex. The correlation between seasonal temperature fluctuations and semen parameters, along with evidence from animal and human studies demonstrating negative effects of heat stress on spermatogenesis and steroidogenesis, underscores the potential impact of global warming on male fertility. The age-independent decline in testosterone levels observed in several studies raises concerns about broader implications for male health. Methodological challenges in isolating the impact of temperature from other lifestyle and environmental factors necessitate further research with rigorous designs to establish causal relationships and quantify the effects of global warming on male reproductive health. The inconsistencies in the observed seasonal variations of testosterone levels highlight the influence of confounding factors such as geographical location, sunlight exposure, and study population characteristics.

This review highlights the significant impact of environmental temperature, particularly global warming, on male reproductive health. While a strong association exists between heat stress and impaired testicular function, establishing a definitive causal link requires further research. Future studies should address the methodological limitations discussed and incorporate sophisticated statistical approaches to account for confounding variables. Investigating the long-term effects of chronic low-level heat exposure is also crucial. Moreover, a more comprehensive understanding of the molecular mechanisms underlying heat-induced testicular damage is needed, particularly regarding the role of ROS and specific cell populations.

This review primarily relies on observational studies and epidemiological data, limiting the ability to definitively establish causality. The heterogeneity of study designs and methodologies across different studies makes direct comparisons challenging. Confounding factors, such as lifestyle choices, nutrition, and exposure to other environmental pollutants, complicate the assessment of temperature's isolated effects. The scarcity of long-term, large-scale studies that comprehensively track environmental temperature trends and male reproductive health outcomes over extended periods limits the ability to draw firm conclusions about the long-term consequences of global warming.