Key regulators of lactation performance in Xinjiang Brown cattle and Chinese Holstein cattle unraveled by multi-omics integration.

This study aimed to elucidate the molecular regulatory mechanisms underlying lactation performance in Xinjiang Brown cattle (XJBC) and Chinese Holstein cattle (CHC). We employed a multi-omics integrative analysis strategy to systematically elucidate these mechanisms by correlating blood transcriptomic and milk/plasma metabolomic data. For each of the four seasons (spring, summer, autumn, and winter), we compared XJBC and CHC using samples from seven individuals per breed. Transcriptome analysis revealed 124, 877, 169, and 81 differentially expressed genes (DEGs) between the two breeds in spring, summer, autumn, and winter, respectively, primarily enriched in biological pathways such as immune response, signal transduction, and metabolic processes. Metabolome analysis indicated that 78, 97, 80, and 50 differentially expressed metabolites (DEMs) were identified in milk, while 80, 173, 48, and 54 DEMs were found in plasma across the respective seasons. Integrated analysis demonstrated that DEGs and DEMs associated with the blood-milk metabolic axis were significantly enriched in signaling pathways, including galactose metabolism, NF-kappa B signaling pathway, and purine/pyrimidine metabolism; those based on the blood-plasma metabolic axis were significantly enriched in pathways such as ABC transporters and ECM-receptor interaction. The results demonstrate that the observed seasonal patterns reflect how breed differences vary across seasons rather than intrinsic seasonal responses of each breed. In conclusion, this study systematically delineates the regulatory modules of lactation performance in XJBC and CHC. The identified DEGs and DEMs provide critical targets and a theoretical foundation for deciphering their molecular mechanisms and advancing molecular breeding.