Tolerance for chronic heat exposure is greater in female than male mice

Purpose: Chronic heat exposure in mice has cellular and physiological effects that improve thermal tolerance [1], but also modifies innate immune responses with potential adverse consequences [2]. While male and female mice are known to respond differently to acute exposure to severe hyperthermia, sex-based differences in responses to chronic moderate heat exposure have not been reported. The major objective of this study was to compare the tolerance of male and female mice for chronic heat exposure. Materials and methods: We used a mouse model of 5-day moderate heat exposure (ambient temperature similar to 37 degrees C) to compare the physiological and cellular heat shock response in male and female mice. Core temperature, heart rate, and activity were monitored telemetrically and heat shock protein levels were measured in brain and lung by western blotting. Results: Adult CD-1 female mice maintained a 1.2 degrees C lower core temperature (38.31 +/- 0.64 versus 39.51 +/- 0.72 degrees C; p = 0.002), experienced less weight loss (1.54 +/- 0.45 versus 4.54 +/- 1.97 g; p = 0.0007), and had improved survival (16/16 survived versus 13/21, p < 0.006) than male mice of the same age. After 5 days of moderate heat exposure Hsp72 levels in brain and lung increased 2.1-fold (p = 0.007) and 5-fold (p = 0.048) in male mice compared with 1.3- (p = 0.054) and 1.5-fold (p = 0.134) in female mice. Conclusions: This study reveals previously unknown and potentially important differences between male and female mice in physiological and cellular responses to chronic heat exposure, which had consequences for survival. Future studies may identify biomarkers of differential heat tolerance and treatments to improve heat tolerance in humans.