Deregulation of the Sod1 and Nd1 genes in mouse fetal oocytes exposed to mono-(2-ethylhexyl) phthalate (MEHP)
Deregulation of the Sod1 and Nd1 genes in mouse fetal oocytes exposed to mono-(2-ethylhexyl) phthalate (MEHP)
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DOI：
10.1016/j.reprotox.2010.04.008
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发表时间：
2010-11-01
影响因子：
3.3
通讯作者：
del Mazo, Jesus
中科院分区：
文献类型：
--
作者：
Bonilla, Edmundo;del Mazo, Jesus
邻苯二甲酸单-（2-乙基己基）酯（MEHP）是众所周知的生殖毒物二酯（DEHP）的活性代谢物。由于这种毒性的不同分子机制尚不清楚，因此在体外培养的小鼠胎儿卵母细胞中评估了MEHP对细胞活力和基因表达的影响。暴露于MEHP 24 h后，卵母细胞存活率显著下降，因此，使用cDNA文库和差异筛选分析MEHP对基因表达变化的影响。在这些分析中，遭受最严重的解除管制的基因对应于编码Cu-Zn超氧化物歧化酶（Sod1）和线粒体呼吸链蛋白（Nd1）的基因。事实上，对转染了Sod1荧光素酶报告基因结构的体细胞进行的功能分析表明，其特异性的MEHP剂量依赖性上调，证实该基因的表达在MEHP的作用下被解除调控。(C) 2010爱思唯尔公司版权所有。
Mono-(2-ethylhexyl) phthalate (MEHP) is the active metabolite of the diester (DEHP), a well-known reproductive toxicant. Since, different molecular mechanisms underlying this toxicity are not well understood, the effects of MEHP on cell viability and gene expression were assessed in murine fetal oocytes cultured in vitro. Oocyte survival decreased significantly after a 24 h exposure to MEHP and hence, the effects of MEHP on changes in gene expression were analyzed using cDNA libraries and differential screenings. In these assays, the genes that suffered the most severe deregulation corresponded to those encoding Cu-Zn superoxide dismutase (Sod1) and a mitochondrial respiratory chain protein (Nd1). Indeed, functional assays on somatic cells transfected with a Sod1 luciferase reporter construct demonstrated its specific MEHP dose-dependent up-regulation, confirming that the expression of this gene is deregulated in response to MEHP. (C) 2010 Elsevier Inc. All rights reserved.