Liver transcriptome dynamics in holstein cows during the periparturient transition

Authors: Bhowmik, Nayan; DA SILVA, MARIANA - University Of Pennsylvania; CASTANEDA, ALEJANDRO - University Of Pennsylvania; Miles, Asha; Li, Congjun; Van Tassell, Curtis; Baldwin, Ransom; RICO, EDUARDO - University Of Pennsylvania; Liu, Ge

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/28/2026
Publication Date: 4/4/2026
Citation: Bhowmik, N., da Silva, M., Castaneda, A., Miles, A.M., Li, C., Van Tassell, C.P., Baldwin, R.L., Rico, E., Liu, G. 2026. Liver transcriptome dynamics in holstein cows during the periparturient transition. Scientific Reports. 16. Article 16227. https://doi.org/10.1038/s41598-026-46925-9.
DOI: https://doi.org/10.1038/s41598-026-46925-9

Interpretive Summary: Dairy cows go through big changes when they give birth, which can affect their health, milk production, and ability to get pregnant again. The liver plays an important role during this time because it helps control how the body uses energy and nutrients. To learn more, we studied liver samples from cows taken three weeks before and one week after calving. After calving, we saw that the liver turned on more genes that help break down fat and protein, make energy, and grow new cells—changes that help meet the high energy demands of making milk. At the same time, genes for storing energy, repairing tissues, and certain growth activities slowed down, showing that the liver was focusing on making energy right away. We also found changes in how cells grow, divide, and handle damage, which may help the cow use more resources for milk production. These findings give us a better understanding of how cows adjust at the molecular level after calving and may help farmers and scientists find new ways to keep cows healthy and productive during this challenging time.

Technical Abstract: During the peripartum phase, dairy cows undergo significant physiological, metabolic, and immunological changes that affect their health, productivity, and reproductive efficiency, as well as that of their calves. The liver plays a crucial role in helping them adapt to these challenges. This study investigated hepatic global transcriptomic changes in peripartum dairy cows in relation to energy balance, fat metabolism, and immune responses. Liver biopsies were collected from six multiparous Holstein cows at 21 days pre-calving (D-21) and 7 days post-calving (D7) for RNA sequencing. The processed RNA-seq reads were aligned to the cattle ARS-UCD2.0 genome assembly. The read counts were used for differential gene expression and co-expression network analyses. We identified 211 DEGs between D-21 and D7 (164 UP, 47 DOWN) using a cutoff of log2FC > |0.5| and a Benjamini-Hochberg-adjusted P-value < 0.05, which were used for pathway enrichment. At D7, cows exhibited pronounced activation of genes related to fat and protein metabolism, energy balance, and cell growth, reflecting the increased energy demands of early lactation. Genes involved in glucan/glycogen/polysaccharide/ketone metabolism, as well as tissue remodeling, were downregulated, consistent with the liver’s prioritization of energy production and metabolic adaptation over growth, repair, and storage functions. KEGG pathway analysis indicated the activation of pathways associated with the endocrine and digestive systems, as well as fat, carbohydrate, and amino acid metabolism, and cell growth after 7 days. Conversely, the p53 signaling pathway regulating the cell cycle and DNA damage response was downregulated at D7, likely promoting cell survival and inhibiting apoptosis in mammary tissue to support enhanced milk production. Co-expression network analysis further confirmed the activation of these biological processes and KEGG pathways. In conclusion, these findings provide valuable insights into the liver transcriptomic adaptations in peripartum dairy cows to meet their metabolic demands during early lactation, offering potential targets for improving health and productivity during this critical period.