Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, United States.
Reprod Toxicol. 2012 Dec;34(4):708-19. doi: 10.1016/j.reprotox.2012.08.010. Epub 2012 Sep 11.
Environmental compounds are known to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a "pesticide mixture" (pesticide permethrin and insect repellent N,N-diethyl-meta-toluamide, DEET) promotes epigenetic transgenerational inheritance of disease and associated DNA methylation epimutations in sperm. Gestating F0 generation female rats were exposed during fetal gonadal sex determination and the incidence of disease evaluated in F1 and F3 generations. There were significant increases in the incidence of total diseases in animals from pesticide lineage F1 and F3 generation animals. Pubertal abnormalities, testis disease, and ovarian disease (primordial follicle loss and polycystic ovarian disease) were increased in F3 generation animals. Analysis of the pesticide lineage F3 generation sperm epigenome identified 363 differential DNA methylation regions (DMR) termed epimutations. Observations demonstrate that a pesticide mixture (permethrin and DEET) can promote epigenetic transgenerational inheritance of adult onset disease and potential sperm epigenetic biomarkers for ancestral environmental exposures.
环境化合物已知可促进疾病的表观遗传跨代遗传。本研究旨在确定一种“农药混合物”（农药氯菊酯和驱虫剂 N，N-二乙基-间-甲苯酰胺，DEET）是否会促进疾病的表观遗传跨代遗传以及精子中的相关 DNA 甲基化表观突变。在胎儿性腺性别决定期间使 F0 代孕雌性大鼠暴露于该混合物中，并在 F1 和 F3 代中评估疾病的发生率。来自农药谱系的 F1 和 F3 代动物的总疾病发生率显着增加。青春期异常，睾丸疾病和卵巢疾病（原始卵泡丢失和多囊卵巢病）在 F3 代动物中增加。对农药谱系 F3 代精子表观基因组的分析确定了 363 个差异 DNA 甲基化区域（DMR），称为表观突变。这些观察结果表明，农药混合物（氯菊酯和 DEET）可促进成年发病疾病的表观遗传跨代遗传，以及潜在的祖先环境暴露的精子表观遗传生物标志物。
