Effects of DEHP on the hepatic expression of a selection of mouse genes related to nuclear receptor signaling.

Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this study we investigated potential mechanisms underlying the impact of di-(2-ethylhexyl)-phthalate (DEHP) on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARα targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and on the Rev-erbα pathway that senses endogenous heme level. Keywords: Treatment effect One-color macroarrays, 4 experimental conditions: Control mice (vehicle treated), mice treated with di-(2-ethylhexyl)-phthalate (DEHP) at 30 mg/kg/day (D30), 180 mg/kg/day (D180) or 1100 mg/kg/day (D1100) for 14 days, Biological replicates: 6 controls, 4 D30, 4 D180, 5 D1100, One replicate per array

邻苯二甲酸酯（Phthalates）是一类广泛用作增塑剂的工业添加剂。除对男性生殖器官发育产生有害影响外，人群研究已证实邻苯二甲酸酯暴露与男性成人生殖道发育异常及代谢综合征之间存在关联。本研究针对邻苯二甲酸二(2-乙基己基)酯（di-(2-ethylhexyl)-phthalate, DEHP）对成年小鼠肝脏的体内影响的潜在机制展开探究。研究对暴露于不同剂量DEHP的成年小鼠的肝脏转录组与代谢组特征进行了平行分析。DEHP调控的肝脏基因主要为过氧化物酶体增殖物激活受体α（PPARα）的靶基因。然而，典型细胞色素P450基因的诱导表达，强烈支持了其他核受体通路的激活，其中包括组成型雄烷受体（Constitutive Androstane Receptor, CAR）。转录组与代谢组特征的整合分析显示，DEHP对血红素合成相关基因及代谢物的影响，与感知内源性血红素水平的Rev-erbα通路的变化存在关联。关键词：处理效应、单色基因芯片（One-color macroarrays）；4种实验分组：对照组（溶剂处理小鼠）、以30 mg/kg/天剂量的邻苯二甲酸二(2-乙基己基)酯（DEHP）处理14天的小鼠（D30组）、以180 mg/kg/天剂量DEHP处理14天的小鼠（D180组）以及以1100 mg/kg/天剂量DEHP处理14天的小鼠（D1100组）；生物学重复：对照组6例，D30组4例，D180组4例，D1100组5例，每块芯片对应1个生物学重复。

搜集汇总

背景与挑战

背景概述

该数据集研究了塑料增塑剂DEHP对成年小鼠肝脏基因表达的影响，重点关注核受体信号通路。实验通过表达谱芯片分析发现，DEHP主要调控PPARα靶基因，并激活CAR等其他核受体通路，同时整合转录组和代谢组数据揭示了其对血红素合成及Rev-erbα通路的关联作用。数据集包含4种处理条件（对照和三种DEHP剂量）的19个生物重复样本，于2009年提交并公开。