Impact of Weight Loss on the Human Sperm Epitranscriptome

Condition(s) studied

Study summary

Increasing evidence suggests that non-communicable diseases such as in particular obesity and its associated metabolic diseases are inherited from parents to children throughout several generations by epigenetic mechanisms. Thus, this environmental stress would induce epigenetic modification in the germ line that once transmitted and maintained in the progeny would induce the development of the parental pathologies. Considering the increasing prevalence of these pathologies worldwide, we urgently need to understand this process in human. Based on published and unpublished data demonstrating that sperm RNAs are vectors of epigenetic inheritance of obesity mouse model, the investigative team hypothesizes that epitranscriptome of obese men play a central role in the paternal epigenetic inheritance of obesity and its associated metabolic diseases as epigenetic vectors in this process.

To validate this hypothesis, the investigative team will use sperm from non-obese and obese men taken before and after surgery weight loss. Thanks to these cohorts, they propose to: (i) compare the epitranscriptome profiles of non-obese and obese men to identify the RNAs molecules which will be either qualitatively or quantitatively epigenetically modulated by obesity; (ii) compare the epitranscriptome profiles of obese men before and after surgery-weight loss to assess the reversibility of the newly acquired RNA modifications.

Giving some answers to this central question will provide not only some clues about the molecular mechanisms involved in this process, elements which might be crucial to stop the spread of this disorder, but will also allow the identification of obese-susceptibility loci which expression may be modulate by environmental factors and consequently able to transmit the disease.

Eligibility

Primary outcome measure(s)

• Impact of weight loss on sperm transcriptome of obese men — Between day 0 and day 365: collection of sperm samples from obese men before bariatric surgery. Between day 370 and 735: collection of the sperm sample from obese men after bariatric surgery. Day 740-800; RNA-seq and data analysis
  To evaluate the impact of weight loss on sperm transcriptome, sperm RNA from obese men will be analyzed by RNA-seq before and one year after bariatric surgery. The supplied samples will be sequenced on the Illumina NextSeq500 and the resulting RNA-Seq Data will be bioinformatically analyzed.

Trial sites (1)

More Institut National de la Santé Et de la Recherche Médicale, France trials in France

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