The Research Institute of the McGill University Health Centre and Department of Medicine (D.B.M.-A., V.P.) and Departments of Biochemistry and Pharmacology and Therapeutics (V.P.), McGill University, Montréal, Québec, Canada H3G 1A4.
Endocrinology. 2015 Jan;156(1):124-33. doi: 10.1210/en.2014-1436.
Exposure to environmental toxicants during fetal development alters gene expression and promotes disease later in life. Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used for the manufacturing of consumer products. Exposure to DEHP has been associated with obesity, asthma, and low T levels. In utero exposure of pregnant dams to DEHP from gestational day 14 until birth resulted in reduced levels of serum T and aldosterone in the adult male offspring. Because DEHP is rapidly cleared from the body, the effects observed in the adult are likely epigenetic in origin. Under the same experimental conditions, we used reduced-representation bisulfite sequencing to assess changes in DNA methylation. We identified hot spots of DNA methylation changes primarily within CpG islands followed by shelf regions of the genome known to control regional gene expression. We also identified epigenomic areas responsive to exposure to environmental levels of DEHP and found the chromosomal region that houses genes controlling immune responsiveness to be a primary target of DEHP. These data suggest that DEHP phthalate exposure early in life induces epigenetic changes that may be linked to altered gene expression and function in the adult.
胎儿发育过程中接触环境毒物会改变基因表达，并促进生命后期的疾病。邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种广泛用于制造消费品的增塑剂。接触 DEHP 与肥胖、哮喘和低 T 水平有关。从妊娠第 14 天到出生，妊娠母体接触 DEHP，导致成年雄性后代血清 T 和醛固酮水平降低。由于 DEHP 会从体内迅速清除，因此在成年期观察到的影响可能源于表观遗传。在相同的实验条件下，我们使用简化代表性亚硫酸氢盐测序来评估 DNA 甲基化的变化。我们发现 DNA 甲基化变化的热点主要位于 CpG 岛内，其次是控制区域基因表达的基因组 shelf 区域。我们还确定了对环境水平 DEHP 暴露有反应的表观基因组区域，并发现控制对免疫反应的基因所在的染色体区域是 DEHP 的主要靶标。这些数据表明，生命早期接触 DEHP 邻苯二甲酸酯会诱导表观遗传变化，这些变化可能与成年期基因表达和功能的改变有关。
