Of mice and women: murine model provides unique insight into mechanisms of exertional heat stroke.

Letter to the EditorOf mice and women: murine model provides unique insight into mechanisms of exertional heat strokeGabrielle E. W. GierschGabrielle E. W. GierschThermal and Mountain Medicine Division, USARIEM, Natick, Massachusetts, United StatesPublished Online:12 Jun 2023https://doi.org/10.1152/japplphysiol.00247.2023MoreSectionsPDF (146 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat to the editor: In recent years, the increased participation of women in athletic endeavors, higher proportions of women in certain occupational settings, as well as the opening of all US Military combat roles to women have highlighted the need for additional research regarding mechanisms of, and risk for, exertional heat illness in women. Interest in the possible influences of female sex hormones on exertional heat illness risk has been (re)ignited. Although some of the influences that female sex hormones, specifically estradiol and progesterone, have on thermoregulation are known, it is unclear how they may play a role in exertional heat stroke (EHS) risk and/or recovery from EHS. Due to the nature of EHS per se, human physiological studies rely on murine models to prospectively elucidate mechanisms related to EHS risk, collapse, and recovery.I was delighted, therefore, to read the manuscript from Rentería et al. (1) in the Journal of Applied Physiology investigating EHS risk in female mice. Uniquely, half of these female mice underwent bilateral ovariectomy (OVX), whereas control mice underwent sham surgery, leaving their ovaries intact. Previous work from this laboratory group has shown that intact female mice outperform their male counterparts in the heat, running farther, and getting hotter—but not leading to increased organ damage (2). Thus, in this follow-up study, Rentería et al. compared ovariectomized and non-ovariectomized female mice using the same EHS protocol. Very interestingly, they found that the ovariectomized mice performed significantly worse than their intact counterparts and that the decrements in performance, temperature, and “thermal tolerance,” were similar to the discrepancies between female and male mice from Garcia et al. (2). Although there were differences in body mass at the time of EHS between groups, the authors suggest the primary mechanism of the differences was related to the impact of female sex hormones. This study also found greater intestinal damage and reduced heat shock protein (HSP) response to EHS in the OVX group.Although the present results from Rentería et al. do not point to specifically which female sex hormone(s) is/are exerting the influences observed, these findings provide valuable insight that can inform human research. In a larger context, the possibility that female sex hormones may be protective against the negative consequences of exercise + heat stress is certainly worth investigating further in humans. More specifically, it will be helpful to gain more information regarding the influences of exogenous female sex hormones in varying contraceptive types/methods and menstrual dysfunction, such as anovulation or amenorrhea, as factors impacting EHS risk and recovery. Although more work is needed in this area, the work by Rentería et al. provided a small step for mice, and a potential leap for women, in furthering our knowledge of sex-based influences on EHS.DISCLAIMERSThe views, opinions, and/or findings contained in this article are those of the authors and should not be construed as an official US Department of the Army position, or decision, unless so designated by other official documentation. Approved for public release, distribution unlimited. Citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement or approval of the products or services of these organizations.DISCLOSURESNo conflicts of interest, financial or otherwise, are declared by the author.AUTHOR CONTRIBUTIONSG.E.G. drafted manuscript; edited and revised manuscript; approved final version of manuscript.REFERENCES1. Rentería LI, Zheng X, Valera I, Machin DR, Leon LR, Laitano O. Ovariectomy aggravates the pathophysiological response to exertional heat stroke in mice. J Appl Physiol (1985). 134: 1224–1231, 2023. doi:10.1152/japplphysiol.00092.2023. Link | ISI | Google Scholar2. Garcia CK, Mattingly AJ, Robinson GP, Laitano O, King MA, Dineen SM, Leon LR, Clanton TL. Sex-dependent responses to exertional heat stroke in mice. J Appl Physiol (1985) 125: 841–849, 2018. doi:10.1152/japplphysiol.00220.2018. Link | ISI | Google ScholarAUTHOR NOTESCorrespondence: G. E. W. Giersch ([email protected].com). Download PDF Previous Back to Top FiguresReferencesRelatedInformation Related ArticlesOvariectomy aggravates the pathophysiological response to exertional heat stroke in mice 25 Apr 2023Journal of Applied Physiology More from this issue > Volume 134Issue 6June 2023Pages 1549-1549 Crossmark Copyright & PermissionsPublished by the American Physiological Society.https://doi.org/10.1152/japplphysiol.00247.2023PubMed37307792History Received 20 April 2023 Accepted 27 April 2023 Published online 12 June 2023 Published in print 1 June 2023 Keywordsexertional heat strokefemale sex hormones Metrics