Sperm Epimutation Biomarkers of Obesity and Pathologies following DDT Induced Epigenetic Transgenerational Inheritance of Disease

Gestating F0 generational female rats were transiently exposed to DDT during fetal gonadal sex determination and the incidence of adult onset pathologies was assessed in the subsequent F1, F2, and F3 generations. In addition, sperm differential DNA methylation regions (DMRs) that were associated with specific pathologies in the F3 generation males were investigated. No pathology was observed in the F1 generation DDT lineage males or females compared with F1 generation controls (vehicle exposure). There was an increase of testis disease and early onset puberty in the F2 generation DDT lineage males. The F3 generation DDT males had significant increases in testis disease, prostate disease, and late onset puberty. The F3 generation DDT females had significant increases in ovarian and kidney disease. Both the F3 generation males and females had significant increases in the frequency of obesity and multiple disease. The F3 generation sperm was collected to examine DMRs for the ancestrally exposed DDT male population. Unique sets of DMRs were associated with late onset puberty, kidney disease, and multiple disease pathologies.

本数据集的研究对象为妊娠状态的F0代雌性大鼠，在其胎儿性腺性别决定阶段对其实施了滴滴涕（DDT）的短暂暴露处理，随后对后续F1、F2及F3代个体的成年发病病理发生率进行了评估。此外，本数据集还针对F3代雄性个体中与特定病理相关的精子差异DNA甲基化区域（differential DNA methylation regions, DMRs）展开了相关探究。与F1代溶剂对照暴露组相比，F1代DDT暴露谱系的雌雄大鼠均未观察到任何病理症状。F2代DDT暴露谱系的雄性个体出现了睾丸疾病与青春期提前的比例升高情况。F3代DDT暴露谱系的雄性个体则表现出睾丸疾病、前列腺疾病以及青春期延迟的发生率显著升高。F3代DDT暴露谱系的雌性个体卵巢疾病与肾脏疾病的发生率显著上升。F3代雌雄个体的肥胖及多种共病发生率均出现显著升高。研究人员收集了该群体F3代雄性个体的精子，以对祖辈暴露于DDT的雄性群体的DMRs进行检测分析。不同的DMR特征分别与青春期延迟、肾脏疾病及多种共病病理相关联。