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This study evaluated the hypothesis that the maternal metabolic stressed status could be inherited to their F1 daughters via epigenetic mechanism. The maternal cow blood β-hydroxybutyric acid (BHB) level (≥0.9 mM/L) was used as an indicator of maternal metabolic stress. Eight newborn daughters’ blood cells were used for methylation comparison and analysis. By Whole Genome Bisulphite Sequencing (WGBS), a total of 1,861 Differentially Methylated Regions (DMRs), including 944 differentially methylated cytosines (DMCs), were identified. Most DMRs were distributed in intronic and intergenic regions, and most of the DMR in promoter regions were hypermethylated. Differentially methylated genes (DMGs) with DMR methylation differences higher than 20% were mainly enriched in metabolism-related pathways. These results suggest that newborn calves’ metabolic pathways were altered, with 64 DMGs being clustered with metabolic signalling by KEGG analysis. Our study revealed the whole epigenetic landscape of calf blood cells and suggested that the maternal metabolic status can affect the embryo’s epigenetic status and metabolic-related pathways in offspring, providing further evidence for epigenetic intergenerational inheritance of metabolic stress in domestic animals. Besides, this study also contributed more evidence to support the Developmental Origins of Health and Disease (DOHAD) theory in large animals.

Comparing the whole genome methylation landscape of dairy calf blood cells revealed intergenerational inheritance of the maternal metabolism