Temperature increases cause transposon-associated DNA damage specifically in spermatocytes

All tissues are susceptible to dramatic increases in temperature; however, developing sperm are particularly sensitive to small temperature fluctuations. In contrast to oogenesis and other developmental processes, mammalian spermatogenesis requires a narrow isotherm of 2-7C below core body temperature. Although failure to thermoregulate spermatogenetic tissue and prolonged exposure to elevated temperatures are linked to male infertility in several organisms, the mechanisms of temperature-induced male infertility is largely unknown. Here we show that upon a brief 2C temperature increase, spermatocytes specifically exhibit temperature-induced transposon mobilization and a 30-40 fold increase in double strand DNA breaks (DSBs) throughout the genome of spermatocytes, which lead to a decrease in male fertility. Using Caenorhabditis elegans to eliminate sex-specific bias, we found that these temperature-induced DSBs are SPO-11 independent and occur only in the spermatocytes of both males and hermaphrodites at all stages of meiotic prophase I. In contrast, oocytes do not display any change in DSB formation upon temperature increases. Further, we found that in males, heat-shock specifically increased both Tc1 transposase expression and Tc1 excision and reinsertion, which causes DSBs in specific sites of the genome. Taken together, our data provide mechanistic insight on how temperature increases specifically compromise the genome integrity of spermatocytes and impairs fertility in males.