Altered sperm DNA methylation provides an epigenetic route from overweight and older men to intergenerational disease transmission.

Overweight and older men exhibit over 38,000 sperm DNA methylation changes linked to neural gene and disease regions, potentially affecting offspring development.

• Why it matters: Understanding how paternal BMI and age influence sperm epigenetics is crucial because these factors are associated with increased risk of neurodevelopmental disorders in children, yet the mechanisms remain unclear.
• What they did: The study used MethylC capture sequencing to analyze sperm from men with elevated BMI, identifying over 38,000 differentially methylated CpGs, especially in regions related to neural functions and early embryonic regulation.
• The result: Findings suggest that sperm methylation alterations associated with higher BMI may impact embryonic transcriptional processes, including placental development, potentially mediating intergenerational disease transmission.