Sant Karilyn E, Dolinoy Dana C, Jilek Joseph L, Sartor Maureen A, Harris Craig
Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, United States.
Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, United States; Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, United States.
Reprod Toxicol. 2016 Aug;63:32-48. doi: 10.1016/j.reprotox.2016.03.042. Epub 2016 May 7.
Mono-2-ethylhexl phthalate (MEHP) is the primary metabolite of di-2-ethylhexyl phthalate (DEHP), a ubiquitous contaminant in plastics. This study sought to determine how structural defects caused by MEHP in mouse whole embryo culture were related to temporal and spatial patterns of redox state and gene expression. MEHP reduced morphology scores along with increased incidence of neural tube defects. Glutathione (GSH) and cysteine (Cys) concentrations fluctuated spatially and temporally in embryo (EMB) and visceral yolk sac (VYS) across the 24h culture. Redox potentials (Eh) for GSSG/GSH were increased by MEHP in EMB (12h) but not in VYS. CySS/CyS Eh in EMB and VYS were significantly increased at 3h and 24h, respectively. Gene expression at 6h showed that MEHP induced selective alterations in EMB and VYS for oxidative phosphorylation and energy metabolism pathways. Overall, MEHP affects neurulation, alters Eh, and spatially alters the expression of metabolic genes in the early organogenesis-stage mouse conceptus.
邻苯二甲酸单-2-乙基己酯（MEHP）是邻苯二甲酸二-2-乙基己酯（DEHP）的主要代谢产物，DEHP是塑料中普遍存在的污染物。本研究旨在确定MEHP在小鼠全胚胎培养中引起的结构缺陷如何与氧化还原状态和基因表达的时空模式相关。MEHP降低了形态学评分，同时增加了神经管缺陷的发生率。在24小时培养过程中，胚胎（EMB）和内脏卵黄囊（VYS）中的谷胱甘肽（GSH）和半胱氨酸（Cys）浓度在空间和时间上波动。MEHP使EMB（12小时）中GSSG/GSH的氧化还原电位（Eh）升高，但在VYS中未升高。EMB和VYS中的CySS/CyS Eh分别在3小时和24小时显著升高。6小时时的基因表达表明，MEHP诱导EMB和VYS中氧化磷酸化和能量代谢途径的选择性改变。总体而言，MEHP影响神经胚形成，改变Eh，并在器官发生早期阶段的小鼠概念胎盘中在空间上改变代谢基因的表达。
