Changes of DNA methylation patterns in mice spermatozoa induced by sodium valproate

Epigenetic effects accompanied with manifestations of toxicity were induced by exposure of some chemicals. Epigenetic effects induced by chemical exposure might be overlooked in mutagenicity test which is one of the toxicity tests. However, the effects have become mentioned as a new safety assessment which might be potential to develop toxicity. Recently, paternal epigenetic information might be transmitted to offspring via spermatozoa. Therefore, it is necessary to investigate the epigenetic effects on spermatozoa. Sodium valproate (VPA) is known to inhibit HDAC, however, the epigenetic effects on spermatozoa have not been detected, to our knowledge. This study was designed to detect epigenetic effects of VPA (100mg/kg/day) without severe reproductive toxicity such as hypospermatogenesis and abnormal morphological spermatozoa. To examine epigenetic effects on spermatozoa induced by VPA, we conducted genome-scale DNA methylation profilings of spermatozoa obtained from C57BL/6 mouse at 12 weeks of age receiving intraperitoneal injection of VPA (100mg/kg/day) and control solution for 14days from 8 weeks of age (VPA, control)