Bisphenol A exposure leads to specific microRNA alterations in placental cells

被引:200
作者
Avissar-Whiting, Michele [1 ]
Veiga, Keila R. [1 ]
Uhl, Kristen M. [1 ]
Maccani, Matthew A. [1 ]
Gagne, Luc A. [1 ]
Moen, Erika L. [1 ]
Marsit, Carmen J. [1 ]
机构
[1] Brown Univ, Dept Pathol & Lab Med, Div Biol & Med, Providence, RI 02912 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
Placenta; MicroRNA; Microarray; Bisphenol A; Epigenetics; DEVELOPMENTAL EXPOSURE; PROSTATE-CANCER; CELLULAR STRESS; IMMUNE-SYSTEM; IN-VITRO; FETAL; EXPRESSION; SUSCEPTIBILITY; MODULATION; ESTRADIOL;
D O I
10.1016/j.reprotox.2010.04.004
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Exposure to bisphenol A (BPA) has been observed to alter developmental pathways and cell processes, at least in part, through epigenetic mechanisms. This study sought to investigate the effect of BPA on microRNAs (miRNAs) in human placental cells. miRNA microarray was performed following BPA treatment in three immortalized cytotrophoblast cell lines and the results validated using quantitative real-time PCR. For functional analysis, overexpression constructs were stably transfected into cells that were then assayed for changes in proliferation and response to toxicants. Microarray analysis revealed several miRNAs to be significantly altered in response to BPA treatment in two cell lines. Real-time PCR results confirmed that miR-146a was particularly strongly induced and its overexpression in cells led to slower proliferation as well as higher sensitivity to the DNA damaging agent, bleomycin. Overall, these results suggest that BPA can alter miRNA expression in placental cells, a potentially novel mode of BPA toxicity. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:401 / 406
页数:6
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