Paternal RNA-mediated epigenetic inheritance of metabolic disorders: impact of weight loss on the human sperm epitranscriptome

ERA-HDHL JFA2 “Nutrition & the Epigenome” (Epigenome)
Paternal RNA-mediated epigenetic inheritance of metabolic disorders: impact of weight loss on the human sperm epitranscriptome
Valerie Grandjean
C3M, Inserm U1065


Partner Organization Partner Country
Institut d'Investigació Biomèdica de GironaSpain
Institute of Pharmacy and BiochemistryGermany

1. Overall project description

1.1 Summary

Increasing evidence suggests that several non-communicable diseases, including obesity and its associated metabolic disorders, are inherited from parents to offspring over several generations by non-genetic mechanisms.

In this context, it has been suggested that parental environmental cues might induce epigenetic modifications in the germ line, which are transmitted to the progeny. Hence, etiological and risk factors that contribute to the insurgence of non-communicable diseases have the potential to drive the development of pathology(ies) in the progeny.Fundamentally, the role of sperm RNA in epigenetic inheritance is not a new phenomenon and has been largely addressed in experimental models. Yet, validation in humans is quite challenging. By combining clinical trial methodology, advances in rodents and cutting-edge computing technologies in bioinformatics, we showed that sperm quality has a strong impact on sperm RNA profiles. Our results indicated that obesity in human might be associated with specific deregulation of sperm RNA. Interestingly these differences tend to disappear after surgery-weight lost, suggesting that this variation in sncRNA profiles induced by obesity can be reversed. Whether this reversion is associated with the reversion of at the 2’‑O‑methylation levels for the subset of sites that tend to be more variable in the obese population needs to be investigated. Further investigation of the role of this sperm RNA specific variation in epigenetic inheritance and their implications in epigenetic inheritance of obesity is under-investigation. If we manage to demonstrate the role of human RNAs through these experiments, we will open new avenues in the identification of genes involved in the development of obesity and its associated diseases. 

Altogether, our work contributes to a better understanding of the molecular mechanisms involved in the non-genetic inheritance of obesity in human which may help to set up an action plan to combat obesity.

1.2 Highlights

Our consortium has now developed the protocol to analyze the epitranscriptome modification from human sperm samples. We have included 40 non-obese and 50 obese patients.  

4. Impact

4.1 List of publications

AuthorsTitleYear, Issue, PPPartners NumberDoiPdf

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf

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This project has received funding from the European Union’s
H2020 Research and Innovation Programme under grant agreement n.696300

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