Altered sperm DNA methylation provides an epigenetic route from overweight and older men to intergenerational disease transmission
Year: 2026
Type: article
Abstract: The occurrence of childhood neurodevelopmental disorders has been steadily increasing for decades, yet we have little understanding of modes of inheritance implicated in these diseases. Epidemiology studies have revealed an association between an elevated paternal Body Mass Index (BMI) and age as factors implicated in increased risk for neurodevelopmental disorders in children. Epigenetic regulation of gene expression by DNA methylation at cytosines is susceptible to environmental, diet, and lifestyle changes. Yet, whether a man’s BMI and age influence the sperm methylome and potentially impact offspring development remains unresolved. Using MethylC capture sequencing, we identified over 38,000 differentially methylated CpGs in the sperm of men with an elevated BMI, with overlap occurring in regions associated with advanced paternal age. These were enriched for neural gene and disease ontologies. Differentially methylated regions localized to transposable elements that can act as active enhancers during human zygotic genome activation, and at gene promoters for early lineage specification. These results suggest that sperm methylome alterations that are linked to an elevated BMI may influence key embryonic transcriptional processes, notably those associated with trophectoderm and placental development.
Institutions: Université de Montréal, University of Ottawa, National Research Council Canada, Ottawa University, Research Institute of the McGill University Health Centre, Health Canada, University of Toronto, CReATe Fertility Centre, McGill Genome Centre, Mercy Children's Hospital, Mercy Research, McGill University Health Centre, McGill University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7222483282