Pregnancy-induced metabolic reprogramming in skeletal muscle: a multi-omics interrogation of transcriptional and metabolic adaptations

• Pregnancy induces profound structural and metabolic remodeling in maternal skeletal muscle, prioritizing fetal nutrient supply over maternal tissue utilization. • Multi-omics profiling reveals myofiber depletion, endothelial expansion, insulin resistance, dysregulated TCA cycle, and impaired ubiquinone biosynthesis. • Skeletal muscle emerges as a critical mediator of pregnancy-induced insulin resistance, offering a new target for GDM prevention. • Findings establish a theoretical foundation for developing skeletal muscle-targeted interventions to prevent gestational diabetes mellitus.