Sex-dependent responses to moderate/low-intensity swimming and loaded ladder-climbing resistance exercise in mdx mice

Duchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration, and the mdx mouse has been widely used to investigate disease mechanisms and therapeutic strategies, including the impact of different exercise modalities and sex-related responses on dystrophic muscle. This study compared moderate/low-intensity swimming and loaded ladder-climbing in male and female mdx, including sedentary control groups for each sex. Animals were subjected to a 4-week swimming (30 min/day, 4 days/week) or a 15-day ladder-climbing resistance protocol (6 sessions, 3 sets of 10 climbs, every 48 h), starting at 30 and 45 days of age, respectively. All groups (male and female sedentary controls, swimming, and resistance-trained mice) were evaluated at 60 days of age. In male mdx mice, swimming reduced serum creatine kinase levels and improved limb functional performance compared to sedentary controls. In contrast, resistance exercise increased diaphragmatic fibrosis and reduced centrally nucleated fibers in biceps brachii in male mdx mice. Resistance-trained males also exhibited lower holding impulse compared to swimming-trained males. Females exhibited a milder response, with superior fatigue resistance, greater mechanical work during climbing, and superior final holding impulse compared to males. These findings demonstrate that exercise outcomes in mdx mice depend strongly on modality, intensity, and sex. Swimming provided functional benefits, while ladder-climbing induced measurable but controlled muscle adaptations, without consistent evidence of widespread damage.