Testicular "Inherited Metabolic Memory" of Ancestral High-Fat Diet Is Associated with Sperm sncRNA Content

Funding: This work was supported by the Portuguese Foundation for Science and Technology: L. Crisóstomo (SFRH/BD/128584/2017), M.G. Alves (PTDC/MEC-AND/28691/2017), UMIB (UIDB/00 215/2020 and UIDP/00215/2020), and ITR (LA/P/0064/2020) and co-funded by FEDER funds (POCI/COMPETE 2020) and by the Portuguese Society of Diabetology: L. Crisóstomo and M.G. Alves (“Nuno Castel-Branco” research grant and Group of Fundamental and Translational Research).publishersversionpublishe

Testicular "Inherited Metabolic Memory" of Ancestral High-Fat Diet Is Associated with Sperm sncRNA Content

Excessive adiposity caused by high-fat diets (HFDs) is associated with testicular metabolic and functional abnormalities up to grand-offspring, but the mechanisms of this epigenetic inheritance are unclear. Here we describe an association of sperm small non-coding RNA (sncRNA) with testicular "inherited metabolic memory" of ancestral HFD, using a transgenerational rodent model. Male founders were fed a standard chow for 200 days (CTRL), HFD for 200 days (HFD), or standard chow for 60 days followed by HFD for 140 days (HFDt). The male offspring and grand-offspring were fed standard chow for 200 days. The sncRNA sequencing from epidydimal spermatozoa revealed signatures associated with testicular metabolic plasticity in HFD-exposed mice and in the unexposed progeny. Sperm tRNA-derived RNA (tsRNA) and repeat-derived small RNA (repRNA) content were specially affected by HFDt and in the offspring of HFD and HFDt mice. The grand-offspring of HFD and HFDt mice showed lower sperm counts than CTRL descendants, whereas the sperm miRNA content was affected. Although the causality between sperm sncRNAs content and transgenerational epigenetic inheritance of HFD-related traits remains elusive, our results suggest that sperm sncRNA content is influenced by ancestral exposure to HFD, contributing to the sperm epigenome up to the grand-offspring

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* avec la participation de J.F. Berthoumieu, J. Biau, J.F. Debras, H. Defrance, J. Favareille, J.F. Mandrin, S. Simon, V. Tourret, F. Villeneuve, J.F. Faivre d'Arcier, M. Jay, A. Masse, J. HarzigNational audienc

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