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.氯菊酯（Permethrin）与N,N-二乙基间甲苯甲酰胺（避蚊胺，DEET）是人类最常用的杀虫剂与驱虫剂。已有研究证实，此类杀虫剂可诱导大鼠发生疾病的表观遗传跨代遗传。本研究采用全表观基因组关联研究（EWAS）的设计框架，旨在筛选与特定跨代遗传疾病相关的潜在精子差异DNA甲基化区域（DMRs）。研究人员对远交系斯普拉格-道利孕鼠（F0代）施加氯菊酯与避蚊胺的复合杀虫剂暴露，其曾孙代（F3代）仅经历了杀虫剂的跨代暴露。研究人员采集罹患单一或多种疾病的跨代成年雄鼠精子，并与未患病个体进行对照比对，以筛选与跨代疾病传播相关的差异DNA甲基化区域。对孕鼠施加氯菊酯与避蚊胺的复合杀虫剂暴露，可导致其后裔曾孙代（F3代）出现睾丸疾病、前列腺疾病、肾脏疾病，且并发多种疾病。值得注意的是，绝大多数与疾病特异性精子DMR相关的基因，此前已被证实与对应疾病的特异性基因存在关联。