GSE111441
Alterations in sperm DNA Methylation, Non-Coding RNA expression, and histone retention mediate Vinclozolin induced epigenetic transgenerational inheritance of disease
Environmental factors have been shown to induce the epigenetic transgenerational inheritance of disease through the germline. This study was designed to investigate vinclozolin induced concurrent alterations of a number of different epigenetic processes including DNA methylation and histone retention in sperm. Gestating female rats were exposed transiently to vinclozolin during fetal gonadal development and then F1, F2 and F3 generation sperm were analyzed. Overall design: The experimental design involved a daily transient exposure of gestating female F0 generation rats during embryonic day E8-E14 to 100 mg/kg per day of vinclozolin in dimethylsulfoxide (DMSO) using intraperitoneal injection. A control generation lineage involved the exposure during day 8-14 of gestation to vehicle DMSO (dimethylsulfoxide) alone. Six different gestating females from different litters for each control and vinclozolin lineage were used. The F1 generation offspring were obtained and aged to 90 day postnatal age and selected males and females bred within the control or vinclozolin lineage. The F2 generation offspring were obtained and aged to 90 days and selected males and females from different litters bred to generate the F3 generation. No sibling or cousin breeding were used to avoid any inbreeding artifacts. All the males were sacrificed at 120 days of age for epididymal sperm collection. The differential DNA methylation regions (DMRs) between the control versus vinclozolin lineages were determined using methylated DNA immunoprecipitation (MeDIP) followed by DNA sequencing (MeDIP-Seq) and bioinformatics analysis. The differential histone retention regions (DHRs) for the F1, F2 and F3 generation for the control versus vinclozolin lineage sperm were analyzed. The procedure involved assessment of differential histone retention sites (DHRs) through a comparison of the control versus vinclozolin lineage sperm using the edgeR analysis similar to that used for the DNA methylation analysis.