基础医学与临床 ›› 2019, Vol. 39 ›› Issue (1): 11-15.

• 研究论文 • 上一篇    下一篇

BDE-209/BPA单暴露对人胚胎干细胞系FY-hES-10早期神经分化中印记基因表达的影响

杜丽丽,李晓梅,李秀英,唐境蔓,陈兢思,陈敦金   

  1. 广州医科大学附属第三医院
  • 收稿日期:2018-01-11 修回日期:2018-05-08 出版日期:2019-01-05 发布日期:2018-12-28
  • 通讯作者: 陈敦金 E-mail:chendunjin@hotmail.com
  • 基金资助:
    国家自然科学基金;广东省自然科学基金博士启动项目;中国博士后科学基金特别资助项目;广州市科技惠民专项项目

Effects of BDE-209 and/or BPA exposure at low dosage on imprinting genes expression in early neural differentiation of human embryonic stem cell line FY-hES-10

  • Received:2018-01-11 Revised:2018-05-08 Online:2019-01-05 Published:2018-12-28

摘要: 目的 探讨十溴联苯醚(BDE-209)和双酚A(BPA)暴露对人胚胎干细胞系(FY-hES-10 cell line)体外早期神经分化中印记基因表达的影响。方法 利用添加小分子抑制剂的方法将FY-hES-10细胞进行神经贴壁诱导,并在培养基中添加低剂量的BDE-209或/和BPA,每24 h换液1次,连续暴露11d。收集诱导分化第11天的细胞检测Nestin阳性率以及印记基因SNRPN、KCNK9、UBE3A和PEG10的表达水平。结果 BDE-209、BPA单独或联合暴露组Nestin的阳性率明显低于对照组(P<0.05)。印记基因SNRPN、KCNK9、UBE3A在BDE-209、BPA单独或联合暴露组表达均明显低于对照组,PEG10在BDE-209 1nmol/L和BDE-209 1nmol/L +BPA 1nmol/L组表达明显低于对照组,而在BPA 1nmol/L组中表达与对照组无明显区别.结论 低剂量BDE-209/BPA单独或联合暴露有可能通过影响胚胎干细胞早期神经分化中印记基因表达从而产生神经发育毒性,BDE-209和BPA联合暴露可能加重神经毒性发育毒性。

关键词: 十溴联苯醚, 双酚A, 胚胎干细胞, 神经分化, 印记基因

Abstract: Objective To study the effects of Decabrominated biphenyl ether (BDE-209) and/or Bisphenol A (BPA) exposure on imprinting gene expression in human embryonic stem cell neural differentiation. Methods Neuroprogenitor cells were derived from human embryonic stem cell line FY-hES-10 cells by using Small-molecule inhibitors, and were exposed to BDE-209 and/or BPA for 11 days. Nestin, imprinting genes(SNRPN, KCNK9, UBE3A and PEG10) expression were detected by immunofluorescence staining and Q-PCR. Results Compared with the solvent control group, the Nestin positive rate of FY-hES-10 derived neuroprogenitors cells in BDE-209 and/or BPA exposure groups were lower. The expression levels of SNRPN,KCNK9 and UBE3A in BDE-209 and/or BPA exposure groups were lower, the expression levels of PEG10 were also lower in BDE-209 1nmol/L and BDE-209 1nmol/L +BPA 1nmol/L gruops with statistically significant differences (P<0.05). The expression level of PEG10 did not change significantly in BPA 1nmol/L exposure group. Conclusions BDE-209 and/or BPA may affect imprinting genes expression resulting in neurodevelopmental toxicity.

Key words: decabrominated biphenyl ether(BDE-209), bisphenol A (BPA), imprinting genes, Human embryonic stem cells, neural differentiation

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