GSE158254
Epigenome-Wide Association Study for Pesticide (Permethrin and DEET) Induced DNA Methylation Epimutation Biomarkers for Specific Transgenerational Disease
Permethrin and N,N-diethyl-meta-toluamide (DEET) are the pesticides and insect repellent most commonly used by humans. These pesticides have been shown to promote the epigenetic transgenerational inheritance of disease in rats. The current study was designed as an epigenome-wide association study (EWAS) to identify potential sperm differential DNA methylation regions (DMRs) for specific transgenerational disease. Outbred Sprague Dawley gestating female rats (F0) were exposed to the pesticide combination including Permethrin and DEET. Their great-grand offspring (F3) were only transgenerationally exposed to pesticides. The transgenerational adult male rat sperm were collected from individuals with single and multiple diseases and compared to non-diseased animals to identify DMRs associated with transgenerational disease transmission. The exposure of gestating female rats to a permethrin and DEET pesticide combination promoted testis disease, prostate disease, kidney disease, and the presence of multiple disease in the subsequent great-grand offspring F3 generation. Interestingly, the majority of the disease specific sperm DMR associated genes were previously found to be linked to relevant disease specific genes. Overall design: Analysis of the transgenerational actions of multiple pesticide chemicals used outbred Sprague Dawley female rats (F0 generation) transiently exposed to pharmacological doses of permethrin (150 mg/kg bodyweight/day) and DEET (40 mg/kg bodyweight/day) during days 8 to 14 of gestation. The F1 generation animals (direct fetal exposure) were bred to generate the F2 generation (direct germline exposure), which were bred to generate the F3 generation (transgenerational so no direct exposure).  The pesticides lineage animals were aged to 1 year and euthanized for pathology and sperm epigenetic analysis. No sibling or cousin breedings (crosses) were used to avoid any inbreeding artifacts. Generally 6–8 founder gestating females from different litters were bred and 25–50 individuals of each sex obtained for each generation.