Abstract
BackgroundExertional heat stroke (EHS) is a condition characterized by central nervous system dysfunction and multi‐organ injury in hyperthermic victims. Most studies addressing EHS pathophysiology are performed in males. This is a concern since there is an increasing participation of females in sports, active military service, and sex‐dependent susceptibilities to EHS. Preclinical data suggest that female mice outperform male mice regarding distance ran, speed, and time to collapse in a model of EHS. Importantly, differences in body mass between males and females do not explain these contrasting heat tolerances. Whether the female sex hormones could account for the superior performance in the heat remains unknown. Our goal was to determine the influence of female sex hormones on performance and thermoregulatory parameters in a preclinical model of EHS.MethodsWe performed ovariectomy (OVX, n=8) or sham (n=8) surgeries in young adult (18 weeks old) female C57/BL6 mice. Ovariectomy was performed by the bilateral removal of the ovaries. To allow for real time monitoring of core temperature during the entire experiment, all mice were implanted with telemetry emitters at the time of ovariectomy/sham surgeries. Upon recovery from surgeries and training (~6 weeks), all mice underwent the EHS protocol in an environmental chamber set at 37.5℃ and 40% relative humidity. Mice exercised on a running wheel until experiencing loss of consciousness.ResultsOvariectomy increased body mass by 10% at the time of EHS (Sham = 25 ± 1 vs OVX = 28 ± 2 g, P<0.05), resulted in 35% shorter distance (Sham = 753 ± 189 vs. 490 ± 87 m, P<0.05), 25% shorter time to collapse (Sham = 126 ± 21 vs. OVX = 95 ± 12 min, P<0.05), and 15% lower final speed (Sham = 9 ± 1 vs. OVX = 7.5 ± 1 m/min, P < 0.05).ConclusionOvariectomy negatively impacts tolerance to EHS. Ovariectomized mice not only displayed a marked decrease in performance during the EHS trial but also gained more mass than their controls. This suggests that female sex hormones are required for a greater tolerance against EHS.
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