Sex-specific extracellular matrix remodeling in skeletal muscle after extended immobilization

Extended periods of disuse can cause changes to the musculoskeletal system, particularly impacting the composition and strength of skeletal muscle. While many studies have investigated changes in muscle phenotype after unloading, majority of these studies were performed on animals of a single genetic background or sex. The effect of muscle immobilization on males compared to females, as well as genetic diversity, is not well understood. The objective of this study was to investigate differential effects of skeletal muscle immobilization in genetically diverse outbred (DO) males and females through large-scale transcriptomic analysis, histopathological, and functional analyses. Transcriptomic analysis revealed both male and female have downregulated metabolism pathways during unloading. Investigation of matrix modifying pathways revealed differential expression of collagen related pathways, not matrix degradation pathways, in males compared to females. Histopathological analysis of collagen and functional analysis of muscle cross sectional area and volume correlated directly with transcriptomic analysis.