Exertional heat stroke (EHS), the most severe manifestation of heat-related illness, affects males and females equally. We previously observed in a model of EHS that the time to loss of consciousness (LOC) was longer in female compared to male mice. Ovariectomy (OVX) abolished this difference and decreased the variability in time to reach LOC. AIMS. We tested the hypotheses that (i) the estrous cycle (EC) phase, which is the rodent equivalent of the menstrual cycle in humans, would influence the time to LOC in our EHS model and (ii) if progesterone replacement in OVX animals would restore the time to LOC. METHODS: Adult C57BL/6 female mice were implanted with telemetry sensors to measure core temperature (TCORE). Following familiarization, mice exercised in a forced wheel running device inside an environmental chamber set at 37.5°C and 40% relative humidity until reaching LOC. We performed cytological determination of the EC; Estrus (E, n=44) was identified by the predominant presence of cornified epithelial cells at high density, while Diestrus (D, n=30) was identified by predominant presence of leukocytes. To evaluate the effect of progesterone, a separate group of animals underwent OVX surgery, and the control group received a vehicle (OVX-C, n=9) while progesterone was delivered via mini osmotic pump for 21 days (OVX-P, n=6) prior to exposure to EHS. RESULTS: In comparison with the E group, D mice required ~18% less time to reach LOC (E: 192.9 ± 36.1 min; D: 169.5 ± 42.8 min; p=0.01), despite achieving lower maximal running speed (Smax; E: 7.4 ± 1.1 m/min; D: 6.6 ± 1.2 m/min, p=0.004), and similar maximal TCORE (E: 42.20 ± 0.21; D: 42.15 ± 0.21 p=0.30). Progesterone delivery increased the uterus mass, a control variable for the progesterone effects (OVX-C: 18.5 ± 9.4 mg; OVX-P: 34.7 ± 8.4 mg, p=0.005), but did not change time to reach LOC (OVX-C: 130.5 ± 28.1 min; OVX-P: 145.6 ± 40.4 min; p=0.40), Smax (OVX-C: 5.2 ± 0.8 m/min; OVX-P: 6.1 ± 1.2 m/min, p=0.11), or maximal TCORE (OVX-C: 42.07 ± 0.34 °C; OVX-P: 42.03 ± 0.32 °C, p=0.81). In conclusion, mice in the diestrus phase reached LOC faster than those in estrus during heat exposure. Progesterone supplementation in OVX mice did not extend time to LOC in this model. These findings may have implications for heat tolerance in women across different menstrual cycle phases and the potential influence of oral contraceptive use on exertional heat illness risk.
Thermal Physiology in Health and Disease: Mechanisms and Therapeutic Applications (Brunel University of London, UK) (2025) Proc Physiol Soc 64, C16
Oral Communications: The estrous cycle phase influences tolerance to exertional heat stroke in mice: Insights into the role of progesterone
Gisienne Reis1, Michele Moraes1, Ali Aldakkan1, Carissa Finley1, Yodit Kiros1, Zoe Schuler1, Malaica Ashley1, Armina Azam1, Diana C. Muller1, Nathaniel Mejia1, Orlando Laitano1
1University of Florida United States
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