Adaptation to full weight-bearing following disuse in rats: The impact of biological sex on musculoskeletal recovery

With the technological advances made to expand space exploration, astronauts will spend extended amounts of time in space before returning to Earth. This situation of unloading and reloading influences human physiology, and readaptation to full weight-bearing may significantly impact astronauts' health. On Earth, similar situations can be observed in patients who are bedridden or suffer from sport-related injuries. However, our knowledge of male physiology far exceeds our knowledge of female's, which creates an important gap that needs to be addressed to understand the sex-based differences regarding musculoskeletal adaptation to unloading and reloading, necessary to preserve health of both sexes. Using a ground-based model of total unloading for 14 days and reloading at full weight-bearing for 7 days rats, we aimed to compare the musculoskeletal adaptations between males and females. Our results reveal the existence of significant differences. Indeed, males experienced bone loss both during the unloading and the reloading period while females did not. During simulated microgravity, males and females showed comparable muscle deconditioning with a significant decline in rear paw grip strength. However, after 7 days of recovery, muscle strength improved. Additionally, sex-based differences in myofiber size existing at baseline are significantly reduced or eliminated following unloading and recovery. Schematic representation of the experimental design and outcomes. It highlights changes in grip strength and bone mineral density during unloading and recovery at normal weight-bearing in males and females.image