Sperm-mediated effects of caloric restriction (CR) on offspring phenotype and epigenotype

肥胖和糖尿病等代谢性疾病的跨代遗传性是医学和营养学领域的研究热点。然而，到目前为止，大多数研究都集中在母亲的营养状况对后代表现的影响上。卡路里限制(CR)是一种已知在多种物种中延长寿命和健康跨度的饮食方案，我们将在研究中使用它对精子的表观遗传效应和表型变异的影响，以及它在后代中转化为代谢表型的影响。这项建议的目的是从表型和/或分子的角度回答以下问题：1)父系CR对雄性后代及其后代的脂肪代谢是否有中介作用？2)对精子的脂肪成分和/或后代的精子性能是否有影响？3)父系CR是否在精子样本中诱导表观遗传效应，并转移到后续的后代幼虫，并可以解释观察到的表型？斑马鱼(Danio Rerio)是一种世代时间短、结构与哺乳动物相似的脊椎动物，这使其成为我们项目的理想模型系统。使用斑马鱼的另一个优势是它是一种外部肥料，通过同时排除胚胎发育过程中非遗传父母的影响而产生大量后代。回答这些前沿研究问题可能通过翻译父亲的表观遗传效应来解释观察到的后代代谢表型的变化。这些结果在动物和人类营养学的基础和应用研究中都具有很高的相关性。

The observed transgenerational heritability of metabolic disorders such as obesity and diabetes is of high research interest in the field of medical science and nutrition. However, until now, most studies focused on the impact of the maternal nutritional status on offspring performance. Caloric restriction (CR), a dietary regimen known to extend life and health spans in a variety of species will be used in our study to investigate its impact on epigenetic effects and phenotypic variation in sperm and its translation into the metabolic phenotype of offspring in subsequent generations. The aim of the proposal is to answer the following questions both from a phenotypic and/ or molecular point of view: 1) Does paternal CR mediate effects on lipid metabolism in male offspring and their subsequent generations? 2) Are there effects on sperm lipid composition and/ or sperm performance in subsequent generations? 3) Does paternal CR induce epigenetic effects in sperm samples, which are transferred into subsequent offspring larvae, and could explain the observed phenotypes?The zebrafish (Danio rerio) is a vertebrate with a short generation time and with structural similarities to mammals, which makes it an ideal model system for our project. One further advantage of using the zebrafish is that it is an external fertilizer, which leads to a large number of offspring by simultaneously excluding non-genetic parental influences during embryo development.The answering of these cutting-edge research questions may explain observed variations in the metabolic phenotype of offspring through translation of paternal epigenetic effects. The results are of high relevance in both basic and applied research in animal and human nutrition.