Maternal Vitamin and Mineral Supplementation Affected Neonatal Gene Expression and Rewired Key Regulatory Genes Underlying Hepatic Metabolism.

We investigated gene regulatory relationships in the neonatal liver to identify potential mechanisms by which maternal vitamin and mineral supplementation during gestation influences developmental programming in heifer calves. Liver transcriptomes were profiled by RNA-Seq in calves collected 30 h after birth from dams fed either a basal diet (CON; = 6) or the basal diet plus a vitamin and mineral premix (VTM; = 6; 113 g·heifer·d), starting 60 days pre-breeding and continuing through gestation. Using DESeq2, we identified 630 DEGs between treatment groups ( ≤ 0.05 and |log2FC| ≥ 0.5). Over-represented pathways included oxidative phosphorylation, AMPK, PI3K/Akt, and FoxO, key regulators of energy homeostasis. We also identified 58 transcription factors (TFs) and 435 differentially connected genes ( ≤ 0.05), suggesting maternal diet induced a regulatory rewiring of TFs and histone deacetylating genes. Gene set enrichment analysis revealed genes positively ranked, such as and , underlying the vitamin digestion and absorption pathway, indicating coordinated upregulation in the VTM group. Conversely, 23 DEGs associated with the OXPHOS KEGG pathway were downregulated in the VTM calves. Further research should explore whether these transcriptional changes are linked to epigenetic modifications established at birth, persist throughout postnatal development, and potentially contribute to multigenerational inheritance.