title: Bisphenol A exposure leads to specific microRNA alterations in placental cells.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, United States.
authors.forename: Michele
authors.initials: M
authors.lastname: Avissar-Whiting
authors.forename: Keila R
authors.initials: KR
authors.lastname: Veiga
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Uhl
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Maccani
authors.forename: Luc A
authors.initials: LA
authors.lastname: Gagne
authors.forename: Erika L
authors.initials: EL
authors.lastname: Moen
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds; D001761:Bleomycin / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010636:Phenols / Q000633:toxicity*; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D001761:Bleomycin; D004247:DNA; D004968:Estrogens, Non-Steroidal; D035683:MicroRNAs; D010636:Phenols; C542542:MIRN146 microRNA, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds