Impact of Weight Loss on the Human Sperm Epitranscriptome

NCT03962699 | Active Not Recruiting

• 2 other identifiers: C18-552019-A00833-54
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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 Based on published and unpublished data demonstrating that sperm RNAs are vectors of epigenetic inheritance of obesity mouse model, the investigative team hypothesizes that epitranscriptome of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.

Conditions

Obesity

Keywords

sperm; Epigenetic; RNA

Outcome Measures

Primary Outcomes (1)

• Impact of weight loss on sperm transcriptome of obese men

  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.

  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

Secondary Outcomes (1)

• Impact of obesity on sperm transcriptome of obese men

  Day 0 to Day 365: collection of sperm samples from obese and non-obese men. Day 740-800; RNA-seq and data analysis

Study Arms (2)

Obese patients selected for bariatric surgery

Normospermic obese patients ((BMI\>40), aged 20-50 years) who will undergo Bariatric surgery.

Control Group: Non obese volunteers

Normospermic obese patients ((BMI\>40), aged 20-50 years

Eligibility Criteria

• Age: 20 Years - 50 Years
• Gender Eligibility Details: Only sperm samples will be collected in this study.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Inclusion Criteria: * selected for a bariatric surgery by a multidisciplinery team * aged between 20-50 years * does not show their opposition to participate in the research study * presented no difficulties in oral and written comprehension of french language. Exclusion Criteria: * men exhibiting less than 1 000 000 spermatozoa/ejaculate * men who are not compliant with the research study

You may qualify if:

• exhibiting a normal BMI from 18 to 25
• aged between 20-50 years
• selected as fertile men in the context of a a medical consultation in Reproduction Biology laboratories
• does not show their opposition to participate in the research study
• presented no difficulties in oral and written comprehension of french language.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

Hopital Archet

Nice, 06202, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

sperm will be collected from each individual

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Valerie Grandjean, Dr

  Institut National de la Santé Et de la Recherche Médicale, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: May 24, 2019
• Study Start: July 20, 2019
• Primary Completion: December 19, 2025
• Study Completion: December 19, 2025
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)