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

Crisostomo, Luis; Bourgery, Matthieu; Rato, Luis; Raposo, Joao F; Batterham, Rachel L; Kotaja, Noora; Alves, Marco G; (2022) Testicular "Inherited Metabolic Memory" of Ancestral High-Fat Diet Is Associated with Sperm sncRNA Content. Biomedicines , 10 (4) , Article 909. 10.3390/biomedicines10040909. Green open access

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Abstract

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.

Type: Article
Title: Testicular "Inherited Metabolic Memory" of Ancestral High-Fat Diet Is Associated with Sperm sncRNA Content
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/biomedicines10040909
Publisher version: https://doi.org/10.3390/biomedicines10040909
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Keywords: High-fat diet; sperm parameters; sncRNA; paternal epigenetic inheritance; inherited metabolic memory
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10147780
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