ABSTRACT

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.

摘要

这项研究评估了母体代谢应激状态可以通过表观遗传机制遗传给他们的 F1 女儿的假设。母体牛血β-羟基丁酸（BHB）水平（≥0.9 mM / L）被用作母体代谢应激的指标。8个新生女儿的血细胞用于甲基化比较和分析。通过全基因组亚硫酸氢盐测序 (WGBS)，共鉴定了 1,861 个差异甲基化区域 (DMR)，其中包括 944 个差异甲基化胞嘧啶 (DMC)。大多数 DMR 分布于内含子和基因间区域，启动子区域中的大多数 DMR 是高甲基化的。DMR甲基化差异高于20％的差异甲基化基因（DMG）主要富集于代谢相关途径。这些结果表明新生小牛的代谢途径发生了改变，通过 KEGG 分析，64 个 DMG 与代谢信号聚集在一起。我们的研究揭示了小牛血细胞的整个表观遗传景观，并表明母体代谢状态可以影响后代胚胎的表观遗传状态和代谢相关途径，为家畜代谢应激的表观遗传代际遗传提供进一步的证据。此外，这项研究还为支持大型动物的健康与疾病的发育起源（DOHAD）理论提供了更多证据。我们的研究揭示了小牛血细胞的整个表观遗传景观，并表明母体代谢状态可以影响后代胚胎的表观遗传状态和代谢相关途径，为家畜代谢应激的表观遗传代际遗传提供进一步的证据。此外，这项研究还为支持大型动物的健康与疾病的发育起源（DOHAD）理论提供了更多证据。我们的研究揭示了小牛血细胞的整个表观遗传景观，并表明母体代谢状态可以影响后代胚胎的表观遗传状态和代谢相关途径，为家畜代谢应激的表观遗传代际遗传提供进一步的证据。此外，这项研究还为支持大型动物的健康与疾病的发育起源（DOHAD）理论提供了更多证据。