Effects of Combined Exercise Training on Modulating Fine Particulate Matter–Induced Skeletal Muscle Damage in Offspring Gestationally Exposed

Background: Fine particulate matter has developmental toxicity, and midgestation is an important period for the development of foetal skeletal muscle. The ability of exercise to modulate skeletal muscle damage in mice exposed to PM_2.5 during gestation remains unclear. Methods: Pregnant C57BL/6 mice were exposed to 50 μg/m³ PM_2.5 for 2 h on five consecutive days starting at embryonic day 12.5 (E12.5d). Combined exercise (treadmill endurance training and weighted ladder resistance training) was followed for 8 weeks in the 4-week-old offspring to verify the regulatory effect of exercise. Results: Offspring exposed to PM_2.5 during gestation showed lower body weight (male, −44.3%; female, −44.8%; p < 0.001), lower skeletal muscle mass (male: TA fibre size, −42%, p < 0.001; TA mass, −37%, p < 0.01; gastrocnemius mass, −46.5%, p < 0.001; female: TA fibre size, −51.6%, p < 0.001; TA mass, −29.8%, p < 0.05; gastrocnemius mass, −40.7%, p < 0.01) and mitochondrial (size decreased for TEM; male: PGC-1α, +78.1%, p < 0.05; Tfam, +591.3%, p < 0.001; FIS-1, +627%, p < 0.001; female: Tfam, +452%, p < 0.01; FIS-1, +345.6%, p < 0.01) dysfunction (at 4 weeks old). They also showed catch-up growth (between 3 and 8 weeks of age; male average weight gain level, +57.9%, p < 0.01; female average weight gain level, +66%, p < 0.05), although they still showed significant mitochondrial damage and impaired glucose metabolism (at 13 weeks of age; male: mitochondrial damage for TEM; Tfam, −46%, p < 0.01; PINK-1, −33.8%, p < 0.05; Parkin, −62%, p < 0.01; PFK-1, −17%, p < 0.05; female: mitochondrial damage for TEM; PFK-1, −28.7%, p < 0.01). Combined exercise was unable to regulate the skeletal muscle system disorder that occurred in male offspring exposed to PM_2.5 during pregnancy. However, it activated the mitophagy (PINK-1, +94.6%, p < 0.05; Parkin, +90.2%, p < 0.001) in female offspring exposed to PM_2.5 during pregnancy, thereby improving mitochondrial damage. Conclusions: Combined exercise had bidirectional, sex-specific effects: Male offspring exhibited reduced responsiveness to exercise, with persistent mitochondrial damage, whereas female offspring showed improved mitochondrial health through increased mitophagy flux.