Liver transcriptome dynamics in Holstein cows during the periparturient transition

During the periparturient phase, dairy cows undergo profound physiological, metabolic, and immunological changes that affect their health, productivity, and reproductive efficiency, with the liver playing a central role in adaptation. In this study, liver transcriptomic changes were assessed in six multiparous Holstein cows by targeting samples approximately 21 d before expected calving date (D-21) and 7 d after calving (D+7) using RNA sequencing. A total of 198 differentially expressed genes (DEGs) were identified between D-21 and D+7 (140 upregulated and 58 downregulated) using |log2[fold-change (FC)]|> 1 and a Benjamini-Hochberg-adjusted P-value < 0.05. At D+7, genes associated with lipid handling, energy metabolism, gluconeogenesis, and cell division were activated, reflecting the elevated energy demands of early lactation. In contrast, genes involved in glycogen, polysaccharide, and ketone metabolism were repressed, indicating metabolic prioritization of energy production overgrowth and storage. KEGG pathway analysis revealed activation of endocrine, digestive, and metabolic pathways, while the p53 signaling pathway controlling the cell cycle and DNA damage response was downregulated, likely promoting cell survival and adaptation. Co-expression network analysis further confirmed activation of these biological processes and pathways. In conclusion, these findings provide insights into liver transcriptomic adaptations that enable periparturient Holstein cows to meet the heightened metabolic demands of early lactation, offering potential targets for improving health and productivity during this critical period.