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Environment/Climate Change

Heat Exposure During Susceptible Windows of Spermatogenesis and Sperm Epigenetic Age Carrie J Nobles* Carrie Nobles Timothy P Canty Pauline Mendola Lindsey M Russo Kaniz Rabeya Karen C Schliep May Shaaban Akanksha Singh Allison M Ring Rachael Hemmert Neil J Perkins C Matthew Peterson Erica B Johnstone James A VanDerslice J Richard Pilsner

Introduction: Spermatogenesis is uniquely susceptible to redox stress, with age-related disruption of the blood-testes barrier associated with changes in sperm DNA methylation linked to reduced fecundity and pregnancy complications. Heat stress may cause similar disruptions, presenting a route through which high temperatures may impair men’s reproductive health.

Methods: We evaluated exposure to high ambient temperatures and sperm epigenetic age in the Folic Acid and Zinc Supplementation Trial (2013-2018). Sperm epigenetic age, the acceleration or deceleration of age-related changes in sperm DNA methylation, was calculated in 1220 men enrolled near Salt Lake City, Utah. Utilizing local hourly temperature data, hours per day exceeding the 98th, 95th, 90th, and 75th percentile thresholds for dry bulb temperature (ambient air) and wet bulb temperature (relative temperature with 100% humidity) were calculated across spermatogenesis and susceptible windows of mitosis, meiosis I+II, spermiogenesis, and spermiation. Generalized linear models adjusted for season, fine particulate matter, and participant characteristics.

Results: During spermatogenesis, an additional 2 hours/day exposure to wet bulb temperatures ≥90th (16.1°C), ≥95th (17.2°C), and ≥98th (17.8°C) percentile thresholds was associated with 0.11 (95% CI 0.04-0.17), 0.18 (95% CI 0.08-0.28) and 0.33 (95% CI 0.12-0.53) years accelerated sperm epigenetic age, respectively. Associations were strongest during the windows of meiosis I+II and spermiogenesis (e.g. 0.08 [95% CI 0.02-0.14] and 0.08 [95% CI 0.03-0.14] years, respectively, for ≥95th percentile). Associations for dry bulb temperature were similar, although moderately attenuated.

Conclusions: Associations of high wet bulb temperatures, capturing impaired efficiency of sweating for cooling body temperature, and accelerated sperm epigenetic age adds evidence that heat-related disruption of spermatogenesis may adversely impact men’s reproductive health.