Investigates sex-dependent recovery of muscle function in mice, suggesting distinct physiological responses.
Background: Musculoskeletal injuries affect >65 million people annually in the U.S. and cost more than 176 billion dollars. After injury, muscle function recovery is highly variable and often incomplete. Many factors affect recovery including biological sex. Our laboratory has shown sex differences in inflammation and maximum force. The effect on other aspects of muscle physiological function is unknown. Therefore, we examined sex differences in measures of physiologic functional recovery including shortening velocity, relaxation time, and fatigue rate after injury. We hypothesized that recovery of physiologic muscle function is sex dependent. Methods: Male and female mice were split into two groups. Mouse gastrocnemius muscle was injected with glycerol (experimental) or saline (control) on day 0. Muscle force production, shortening velocity, relaxation time and muscle fatigue testing was performed 3 days (n=34) and 12 days (n=45) after injection, followed by hind-limb muscle collection and preservation for histological and molecular analysis. Molecular analyses include tissue necrosis, inflammation, and regeneration. Data were analyzed with SPSS using a two-way ANOVA. Results: The improvement in contraction velocity (p< 0.05), and relaxation time (p< 0.05) was significant in the female groups only. Fatigue data, histological and molecular analysis was also suggestive of sex differences. Some molecular analysis continues to delineate molecular causes. The current findings agree with our previous analysis that females recover function faster than males. The faster female recovery appears related to inflammation. Conclusions: The timeline of muscle recovery is different between the male and female groups and repair and regeneration continues at 12 days. This suggests that clinical interventions can be applied during this time to affect outcomes. Sex-based differences inflammation, fibrosis, and muscle repair occurred. Estrogen is a likely causative factor. Our laboratory is currently examining the role of estrogen and exercise in the muscle rehabilitation process. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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