Oral Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

The role of sperm miRNAs in the paternal inheritance of diabetes and obesity development (143433)

Katharina Laurent 1 2 , Raffaele Teperino 1 2 , Martin Hrabě de Angelis 1 2 3 4 , David Skerrett-Byrne 1 5 6 7 , Johannes Beckers 1 2 4 8
  1. Helmholtz Munich, Neuherberg, Germany
  2. German Center for Diabetes Research (DZD, Neuherberg, Germany
  3. German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Deutschland
  4. Chair of Experimental Genetics, TUM School of Life Sciences, Technische Universität München, Freising, Germany
  5. Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
  6. School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia
  7. Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Vic, Australia
  8. INFRAFRONTIER ERIC, Neuherberg, Germany

Background: Evidence shows that metabolic diseases such as obesity and diabetes are more pronounced in the offspring of malnourished parents. Studies suggest that predisposition can be inherited via epigenetic information in gametes. This has sparked growing interest in small regulatory RNAs in sperm as carriers of epigenetic inheritance. However, the functional annotation of dysregulated sperm microRNAs (miRNAs) in obesity and diabetes remains limited.

Method: This work addresses this gap by analysing publicly available datasets of diet-regulated sperm miRNAs and linking them to genes functionally associated with obesity and diabetes with an in silico approach. We systematically identified diet-responsive sperm miRNAs and overlapped their predicted targets with genes associated with metabolic phenotypes, as catalogued by the International Mouse Phenotyping Consortium (IMPC).

Results: With a sequence-based approach we uncovered 11,272 and 6,528 potential target genes for miRNAs regulated by the acute and chronic HFD interventions, respectively. By overlapping these predicted target genes of sperm miRNAs with our IMPC-derived list of obesity and diabetes associated genes, we identified more than 1,000 HFD predicted response genes. To support further research, we provide the field with the ShinyFatSperm App, which facilitates the functional interpretation of diet-regulated sperm miRNAs and enables users to explore their roles in the intergenerational transmission of metabolic disease risk.

Conclusion: Our findings reinforce the concept that paternal dietary exposures can influence offspring health through epididymal- and sperm-borne miRNAs. This work provides a roadmap for hypothesis-driven investigation into the intergenerational inheritance of metabolic disease and highlights the urgent need for translational strategies to interrupt this cycle.