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体营养状况对子代性能的影响上。热量限制（CR），一种已知可以延长多种物种寿命和健康的饮食方案，将在我们的研究中用于研究其对精子表观遗传效应和表型变异的影响，以及其对后代代谢表型的转化。该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是否介导雄性后代及其后代的脂质代谢作用？2)对后代的精子脂质组成和/或精子性能有影响吗？3)父本CR是否在精子样本中诱导表观遗传效应，并将其转移到后代幼虫中，从而解释所观察到的表型？斑马鱼（Danio rerio）是一种产生时间短，结构与哺乳动物相似的脊椎动物，这使它成为我们项目的理想模型系统。使用斑马鱼的另一个优点是，它是一种外部肥料，在胚胎发育过程中，通过同时排除非遗传亲本影响，可以产生大量后代。这些前沿研究问题的答案可以解释通过翻译父本表观遗传效应观察到的后代代谢表型的变化。研究结果对动物和人类营养的基础研究和应用研究具有重要意义。

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.