Impact of the Estrous Cycle on Loss of Consciousness and Survival in Exertional Heat Stroke in Mice.

Abstract

Exertional heat stroke (EHS) is the most severe manifestation of heat-related illness. We previously observed, in a mouse model of EHS, that the time to loss of consciousness (LOC) was longer in females compared with males. Ovariectomy abolished this sex difference and decreased the variability in time to reach LOC in our model. Here, we tested the hypothesis that the estrous cycle (EC) phase, the rodent equivalent of the menstrual cycle in humans, would influence the time to LOC in our mouse EHS model. Adult C57BL/6 female mice were implanted with telemetry sensors to measure core temperature (T CORE ). Following familiarization and cytological determination of the EC, mice exercised in a forced wheel running device inside an environmental chamber set at 37.5°C and 40% relative humidity until reaching LOC. Estrus (E) was identified by the predominant presence of cornified epithelial cells, while Diestrus (D) was identified by the predominant presence of leukocytes. In comparison with mice in the E group ( n = 44), mice in D ( n = 30) reached LOC ~18% faster (D: 169.5 ± 42.8 min; E: 192.9 ± 36.1 min; P = 0.01), despite a lower maximal running speed (Smax; E: 7.4 ± 1.1 m·min -1 ; D: 6.6 ± 1.2 m·min -1 ; P = 0.004). However, mice in E demonstrated a higher mortality rate post-EHS compared with mice in D. The EC influences tolerance to ans survival following EHS in mice.