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

• Applicant: Dr. Constance Nebendahl
• Subject Area: Nutritional Sciences
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 265378825

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.

• DFG Programme: Research Fellowships
• International Connection: Sweden
• Host: Professorin Dr. Simone Immler