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双-(2-乙基己基)邻苯二甲酸酯诱导的小鼠睾丸毒性中的动态表观遗传变化。

Dynamic epigenetic changes involved in testicular toxicity induced by di-2-(ethylhexyl) phthalate in mice.

机构信息

Department of Pediatric Urology Surgery, Children's Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Basic Clin Pharmacol Toxicol. 2010 Feb;106(2):118-23. doi: 10.1111/j.1742-7843.2009.00483.x. Epub 2009 Nov 11.

Abstract

The aim of this study was to analyse epigenetic (specifically, DNA methylation) change in testes induced by maternal exposure to di-2-(ethylhexyl) phthalate (DEHP) in mice. Testicular dysgenesis syndrome was induced in foetuses by maternal exposure to DEHP. High-performance liquid chromatography was performed to analyse DNA methylation status, and expression levels of the DNA methyltransferases were examined by quantitative real-time polymerase chain reaction and western blotting. DEHP significantly had more than 10% relative increase in the global DNA methylation and also increased DNA methyltransferases' expression. Changes in DNA methylation may play an important role in abnormal testicular function caused by environmental factors such as maternal exposure to DEHP, which may be one possible mechanism of DEHP-mediated testicular toxicity.

摘要

本研究旨在分析母体暴露于邻苯二甲酸二(2-乙基己基)酯(DEHP)对小鼠睾丸的表观遗传(特别是 DNA 甲基化)变化。通过母体暴露于 DEHP 诱导胎儿睾丸发育不良综合征。采用高效液相色谱法分析 DNA 甲基化状态,并通过定量实时聚合酶链反应和蛋白质印迹法检测 DNA 甲基转移酶的表达水平。DEHP 显著使全基因组 DNA 甲基化增加超过 10%,并增加了 DNA 甲基转移酶的表达。DNA 甲基化的变化可能在母体暴露于 DEHP 等环境因素引起的睾丸功能异常中发挥重要作用,这可能是 DEHP 介导的睾丸毒性的一种可能机制。

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