Journal
REPRODUCTIVE TOXICOLOGY
Volume 29, Issue 4, Pages 401-406Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2010.04.004
Keywords
Placenta; MicroRNA; Microarray; Bisphenol A; Epigenetics
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Funding
- National Institutes of Health NCRR [P20 RR018728, P20 RR016457]
- National Institutes of Health-National Institute of Environmental Health Sciences [P42 ES013660]
- National Science Foundation [0554548]
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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.
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