Genome-wide microRNA expression profiling in placentas from pregnant women exposed to BPA.
Genome-wide microRNA expression profiling in placentas from pregnant women exposed to BPA.
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DOI：
10.1186/s12920-015-0131-z
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发表时间：
2015-09-07
影响因子：
2.7
通讯作者：
Guida M
中科院分区：
文献类型：
--
作者：
De Felice B;Manfellotto F;Palumbo A;Troisi J;Zullo F;Di Carlo C;Di Spiezio Sardo A;De Stefano N;Ferbo U;Guida M;Guida M
双酚A （BPA）是一种已知具有内分泌干扰潜力的环境化合物。双酚A具有表观遗传效应，可以调控microRNAs的表达；这种表观遗传标记可以诱导基因表达的上下变化，这种变化可能持续一生。孕妇暴露于双酚A （BPA）已被记录在案，但怀孕期间暴露于双酚A对后代发育的影响尚未得到广泛研究。因此，本研究的目的是全面了解因胎儿畸形而接受治疗性流产的孕妇胎盘转录组中microrna的变化，并将妊娠期暴露于BPA对这些发育变化的影响联系起来。我们使用微阵列技术对暴露于BPA的孕妇胎盘中全基因组miRNA的表达进行了比较分析，以鉴定畸形胎儿胎盘中异常表达的miRNA。用qPCR方法确认微阵列样品中差异表达mirna的表达变化。此外，我们应用各种生物信息学工具预测鉴定出的miR-146a的靶基因，探索其生物学功能和下游通路。我们发现，生活在污染地区并因胎儿畸形而进行治疗性流产的孕妇的胎盘中miR-146a显著过表达，并与BPA积累显著相关。此外，我们运用多种生物信息学工具预测miR-146a的靶基因，探索其生物学功能和下游通路。我们首次发现，在人类中，miR-146a显著过表达，并与胎盘中BPA的积累显著相关。我们的研究结果表明，mirna可能是阐明环境疾病机制的潜在生物标志物。
Bisphenol A (BPA) is an environmental compounds is known to possess endocrine disruption potentials. Bisphenol A has epigenetic effects as deregulated expression of microRNAs; such epigenetic marks can induce up/down alterations in gene expression that may persist throughout a lifetime. Bisphenol A (BPA) exposure has been documented in pregnant women, but consequences for development of offspring after BPA exposure during pregnancy are not yet widely studied. Therefore, the aim of this study was to gain a comprehensive understanding of microRNAs changes in the placenta transcriptome from pregnant women subjected to therapeutic abortion for fetal malformation and correlate the impact of gestational exposure to BPA on these developmental changes. We performed a comparative analysis of genome wide miRNA expression in placentas from pregnant women exposed to BPA using microarray technology to identify miRNAs which were aberrantly expressed in placentas from malformed fetuses. The expression changes of differential expressed miRNAs in the samples used for microarray were confirmed by qPCR . Beside, we applied various bioinformatics tools to predict the target genes of the identified miR-146a and explore their biological function and downstream pathways. We found that miR-146a was significant overexpressed and correlated significantly with BPA accumulation in the placenta from pregnant women living in a polluted area and undergoing therapeutic abortion due to fetal malformations. Beside, we applied various bioinformatics tools to predict the target genes of miR-146a and explore their biological function and downstream pathways. For the first time, we found, in humans, that miR-146a was significant over-expressed and correlated significantly with BPA accumulation in the placenta. Our results lead to the suggestion that miRNAs could be potential biomarkers to clarify the mechanisms of environmental diseases.