Kizilaslan Mehmet, Braz Camila U, Townsend Jessica, Taylor Todd, Crenshaw Thomas D, Khatib Hasan
Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Int J Mol Sci. 2025 Jul 3;26(13):6412. doi: 10.3390/ijms26136412.
Despite two extensive reprogramming events during early embryogenesis and gametogenesis, epigenetic information can be passed to the next generations, which constitutes the transgenerational epigenetic inheritance of phenotypes. Considering its utmost importance, there have been few studies focused on the transgenerational effects of dietary interventions, such as methionine supplementation, in livestock. Using whole-genome bisulfite sequencing, we implemented a single-base resolution differential methylation analysis for the F3 and F4 descendants of control vs. methionine-supplemented F0 twin-pair rams. Based on the results of our previous study on F0, F1, and F2 generations, we compared current results of 2981 and 1726 differentially methylated cytosines (DMCs), as well as 798 and 553 unique differentially methylated genes (DMGs), in F3 and F4, respectively. We identified 41 DMGs that exhibited transgenerational epigenetic inheritance (TEI-DMGs) across four generations and 11 TEI-DMGs across five generations. Finally, we estimated the effect size of F0 diet group on F3 and F4 growth and fertility-related phenotypes, providing evidence for transgenerational effects of diet group accompanying inherited differentially methylated genes. Here, for the first time using gene-level and phenotypic data, we demonstrate that a moderate dietary intervention can exert long-lasting transgenerational effects on offspring phenotypes extending beyond the F2 generation in sheep.
尽管在早期胚胎发育和配子发生过程中发生了两次广泛的重编程事件，但表观遗传信息仍可传递给下一代，这构成了表型的跨代表观遗传遗传。鉴于其至关重要性，针对诸如补充蛋氨酸等饮食干预对家畜的跨代影响的研究却很少。我们使用全基因组亚硫酸氢盐测序技术，对对照组与补充蛋氨酸的F0双胞胎公羊的F3和F4后代进行了单碱基分辨率的差异甲基化分析。基于我们之前对F0、F1和F2代的研究结果，我们分别比较了F3和F4中2981个和1726个差异甲基化胞嘧啶（DMC）以及798个和553个独特的差异甲基化基因（DMG）的当前结果。我们鉴定出41个在四代中表现出跨代表观遗传遗传（TEI-DMG）的DMG和11个在五代中表现出跨代表观遗传遗传的TEI-DMG。最后，我们估计了F0饮食组对F3和F4生长及繁殖相关表型的效应大小，为伴随遗传的差异甲基化基因的饮食组跨代效应提供了证据。在此，我们首次使用基因水平和表型数据证明，适度的饮食干预可对绵羊后代的表型产生持久的跨代效应，这种效应延伸至F2代之后。
