Low paternal dietary folate alters the sperm epigenome and is associated with negative pregnancy outcomes

Epidemiological studies suggest that a father’s diet can influence offspring health. A proposed mechanism for paternal transmission of environmental information is via the sperm epigenome. The epigenome includes heritable information such as DNA methylation. We hypothesized that the dietary supply of methyl donors would alter epigenetic reprogramming in sperm. This hypothesis was examined by feeding male mice a folate deficient (FD) and folate sufficient (FS) diets and then generating and analyzing DNA methylation profiles of their sperm. C57BL/6 males were fed either the FS or FD diet throughout life (FS, n=32; FD, n=35; 2-3 month old). Pooled gene promoter DNA methylation profiles were generated from the sperm of three FS males and four FD males using the method of MeDIP (Methylated DNA Immunoprecipitation) followed by microarray hybridization.