Project description:DE-71, a commercial mixture of the polybrominated diphenyl ethers (PBDEs), is used as flame retardant and the potential exposure to PBDEs is an emerging public health concern. It has been clarified that long term exposure to PBDEs induces hepatocellular carcinoma in mouse. In this study, we analyzed how DE-71 impacts on DNA methylation in hepatocellular carcinoma.
Project description:RNA sequence analysis showed that PBDE47 had estrogenic activity through cell cycle regulation, and PBDE100 and PBDE153 had anti-estrogenic activity throguth ER and AhR cross talk.
Project description: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.
