Exposure of Young Mice to Atmospherically Relevant PM_2.5Has Sex-Dependent Long-Lasting Impacts on the Skeletal Muscle System

The negative effects of particulate matter up to 2.5 µm in diameter (PM_2.5) and their mediating mechanisms have been studied in various tissues. However, little is known about the mechanism and long-term tracking underlying the sex-dependent effects of PM_2.5on skeletal muscle system modulation. During youth, skeletal muscle grows rapidly and develops at its highest rate. Here we explore how exposure to atmospherically relevant levels of artificial PM_2.5 affects the skeletal muscle system in 4-week-old C57BL6 mice according to sex and track the effects for 15 months post-exposure. We found that PM_2.5retarded muscle fiber growth and caused mitochondrial damage by modulating factors related to mitochondrial kinetics. However, the effects of PM_2.5 on the modulation of the skeletal muscle system differed by sex and post-exposure time. The negative impacts of PM_2.5on skeletal muscle continued until they were overwhelmed by aging-related oxidative stress and inflammation, which were more severe in older PM_2.5-exposed female mice compared with male mice. Older PM_2.5-exposed female mice, but not older PM_2.5-exposed male mice, exhibited obesity-related phenotypes in the form of increased weight and fat mass. Overall, initial exposure to PM_2.5 affected the skeletal muscle system with long-lasting impacts that differed according to sex.