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

所观察到的代谢紊乱如肥胖和糖尿病的跨代遗传性在医学科学和营养学领域具有高度的研究兴趣。然而，到目前为止，大多数研究都集中在母体营养状况对后代性能的影响。热量限制（CR）是一种已知可延长多种物种寿命和健康寿命的饮食方案，将在我们的研究中使用，以研究其对精子表观遗传效应和表型变异的影响及其在后代中转化为后代代谢表型的影响。该提案的目的是从表型和/或分子的角度回答以下问题：1）父方CR是否介导对雄性后代及其后代脂质代谢的影响？2)对后代的精子脂质组成和/或精子性能是否有影响？3)父亲CR诱导精子样本中的表观遗传效应，这是转移到随后的后代幼虫，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点是它是一种外部肥料，在胚胎发育过程中排除了非遗传的亲本影响，从而产生大量的后代。这些前沿研究问题的答案可以解释通过翻译父系表观遗传效应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的基础和应用研究中具有高度相关性。

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.