ABSTRACT BACKGROUND: Female military integration may enhance stress exposure risks, including thermal strain. Men and women differ in heat stress response mechanisms, which may be sexually-regulated. A primary thermogenic organ, skeletal muscle may contribute towards these thermoregulatory divergencies; however, it is unclear how this may be reflected within its proteomic landscape. PURPOSE: The purpose of this investigation was to characterize the musculoskeletal proteomic response after acute heat tolerance test (HTT) performance to compare: (1) between sexes within a naïve state (AIM 1), (2) within sexes across acclimation (AIM 2), and (3) between thermally tolerant and intolerant classifications (AIM 3). METHODS: Fourteen men (n = 7, age: 21.5 ± 0.68yrs, height: 178.97 ± 7.95cm, mass: 70.06 ± 12.22kg, VO2max: 52.86 ± 2.35ml·kg-1·min-1) and women (n = 7, age: 24.24 ± 1.43yrs, height: 131.71 ± 1.76cm, mass: 59.87 ± 0.80kg, VO2max: 45.97 ± 2.57ml·kg-1·min-1) completed a 5-day HA protocol within an environmental chamber (40 0C, 40% rH). Both before (naïve) and after (acclimated) HA, participants performed an acute HTT until either reaching (1) the 39.5 0C thermal threshold or (2) volitional fatigue. Musculoskeletal samples were harvested for protein extraction, quantification, and digestion prior to untargeted proteomic analysis. Physiological, perceptual, and performance metrics were statistically analyzed using (1) dependent samples t-tests for assessment across acclimation and (2) independent samples t-tests for assessment across groups with p ≤ 0.05. Protein expression was quantified using an uncorrected (p < 0.05) t-test and further assessed for protein-protein interactions. RESULTS: Insignificant differences (p > 0.05) were observed in HTT performance and thermoregulatory protein expression between naïve men and women. POSTHA HTT performance was significantly extended compared to PREHA (p = 0.001) with sex-specific enhancements for females compared to males (MPOSTHA, p = 0.014) and across acclimation (FPREHA, p = 0.029) despite smaller POSTHA protein network expansion. Insignificant differences (p > 0.05) were observed for both PREHA and POSTHA HTT performance between thermally tolerant and intolerant individuals despite noted divergencies in stress-related protein expression. CONCLUSION: Musculoskeletal contributions towards heat stress responses and acclimatory adaptations were demonstrated through protein interactions and network expansion which may underline the health- and performance-related benefits of HA.
