Oxidative DNA damage impairs global sperm DNA methylation in infertile men

Abstract

Purpose: Methylation of sperm DNA is impaired in many infertile men potentially adversely effecting reproductive outcomes. In somatic cells oxidative damage to DNA and hyperhomocysteinaemia are linked with DNA hypomethylation. The objective of this study was to investigate if these pathologies also impair sperm DNA methylation. Methods: The relationship between sperm DNA quality, oxidative stress and serum homocysteine was analysed at study entry and after 3 months of antioxidant treatment. Results: Overall a significant negative correlation was observed between sperm DNA methylation and sperm DNA fragmentation, as well as seminal reactive oxygen species (ROS) production. Sperm DNA methylation was not significantly related to serum homocysteine concentrations. Administration of an antioxidant supplement produced a significant fall in seminal ROS levels and sperm DNA fragmentation, while increasing sperm DNA methylation. Conclusions: These results suggest that oxidative stress related damage to sperm DNA impedes the process ofmethylation, while antioxidant supplementation appears to have the potential to reduce DNA damage and normalize sperm DNA methylation.