To investigate the genetic regulatory mechanism of supplementary feeding on muscle development in Oula sheep, we employed transcriptomic analysis to explore the differentially expressed genes (DEGs) in the longissimus dorsi muscle of Oula sheep at different ages under conditions of supplementary feeding and non-supplementary feeding, as well as the significantly enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways of DEGs. Moreover, by combining with the method of weighted gene co-expression network analysis, we screened for the potential hub genes that might play crucial roles. The results demonstrated that the CD4 and ICAM1 genes and the PI3K-Akt signaling pathway might exert important functions during the lamb stage. At the growth stage, the AGL, PGM2L1, PRKAA2, NEDD4, and GBE1 genes might serve as core genes to regulate the growth of skeletal muscle in Oula sheep after supplementary feeding through signaling pathways such as starch and sucrose metabolism and insulin signaling pathway. This outcome provides a molecular-level interpretation of the regulatory mechanism of supplementary feeding on muscle growth and development in Oula sheep at different ages, offering a theoretical basis for the further improvement of the meat quality of Oula sheep and the enhancement of the quality of livestock products in the Qinghai–Tibet Plateau region.

To investigate the gene regulatory mechanisms underlying muscle development in Oula sheep at different growth stages, under supplementary feeding, particularly the shift in core regulatory mechanisms governing muscle development from the fetal stage to the postnatal period, we conducted transcriptomic sequencing and comparative analysis of the longissimus dorsi muscle collected during the embryonic, lamb, and adult stages. Differentially expressed genes (DEGs) potentially associated with muscle growth and development were identified across various age phases. Furthermore, Short Time-series Expression Miner (STEM) analysis was employed to decipher the temporal expression patterns of these DEGs. The results indicated that metabolic processes related to carbohydrates, energy, and amino acids were enhanced with increasing age in Oula sheep muscle. Comparative analysis between different growth stages revealed that the functional enrichment of DEGs was directly associated with changes in skeletal muscle development, with significant enrichment in biological pathways such as ECM–receptor interaction, PI3K-AKT signaling pathway, and protein digestion and absorption. Additionally, we observed that PTPRC, IL10, NDUFAB1, BUB1, BUB1B, CDK1, ITGB3, and ITGB2 may play pivotal roles in the regulation of muscle growth and development across different stages in Oula sheep. These findings provide theoretical support for the understanding of the genetic regulatory mechanisms underlying muscle development in Oula sheep.