Polybrominated diphenyl ethers (PBDEs) exposure during pregnancy alters microRNA expression profile in rat placenta

Polybrominated diphenyl ethers (PBDEs) are well-known endocrine disrupting chemicals (EDCs), and have been found to affect reproduction and development. The placenta, as the interface between maternal and fetal circulation, is constantly exposed to maternal EDCs. The present study investigated PBDEs-induced changes in miRNAs in rat placenta, and the potential mechanism of developmental toxicity. Female rats were exposed to 500 mg/kg/day decabromodiphenyl ether (BDE-209) from gestational day 0 (GD 0) to GD 20. miRNAs were isolated from the placenta on GD 20. Expression of miRNAs were analyzed using next-generation sequencing, and validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 55 miRNAs were found changed significantly in the exposure group, among which 46 were down-regulated and 9 were up-regulated. Rno-miR-17-5p, rno-miR-503-5p, rno-miR-374-5p, rno-miR-369-3p, rno-miR-29a-3p were confirmed to be down-regulated, rno-miR-148a-3p was validated up-regulated in the exposure group. The bioinformatic analysis showed that the predicted miRNAs target genes were involved in vascular endothelial growth factor (VEGF) signaling pathway, suggesting the role of PBDEs-induced developmental toxicity via the interference with the angiogenesis process in placenta. Our findings demonstrated evidence of altered microRNA expression with PBDEs exposure, thus providing novel insights into mechanisms of PBDEs developmental toxicity.多溴二苯醚（Polybrominated diphenyl ethers, PBDEs）是一类公认的内分泌干扰物（endocrine disrupting chemicals, EDCs），已被证实可对机体生殖与发育过程造成影响。胎盘作为母胎循环的生理交换界面，持续暴露于母体来源的内分泌干扰物中。本研究探究了十溴二苯醚（BDE-209）暴露对大鼠胎盘中微小RNA（microRNA, miRNA）表达的影响，及其介导发育毒性的潜在机制。实验中，雌性大鼠自妊娠第0天（GD 0）至妊娠第20天（GD 20）每日以500 mg/kg的剂量暴露于十溴二苯醚（BDE-209）。于GD 20时从胎盘中分离提取微小RNA，通过下一代测序技术分析其表达谱，并采用逆转录定量聚合酶链式反应（RT-qPCR）进行验证。结果显示，暴露组中共筛选出55个差异表达的微小RNA，其中46个表达下调，9个表达上调。经RT-qPCR验证，rno-miR-17-5p、rno-miR-503-5p、rno-miR-374-5p、rno-miR-369-3p、rno-miR-29a-3p的表达显著下调，而rno-miR-148a-3p的表达显著上调。生物信息学分析表明，上述差异微小RNA的预测靶基因显著富集于血管内皮生长因子（vascular endothelial growth factor, VEGF）信号通路，提示多溴二苯醚（PBDEs）或可通过干扰胎盘血管生成过程引发发育毒性。本研究结果证实了多溴二苯醚暴露可改变胎盘中微小RNA的表达谱，为阐明多溴二苯醚的发育毒性机制提供了全新的研究视角。