十溴联苯醚暴露对人胚胎干细胞分化潜能的影响  

Effects of BDE-209 exposure on differentiation capacity of human embryonic stem cells

作　　者：杜丽丽[1] 匡丽云[1] 汤雯婷 陈敦金[1] 

机构地区：[1]广州医科大学附属第三医院广东省产科重大疾病重点实验室广东普通高校生殖与遗传重点实验室,广州510150

出　　处：《卫生研究》2016年第3期350-355,共6页Journal of Hygiene Research

基　　金：国家自然科学基金(No.81370775.81302399);广东省自然科学基金博士启动项目(No.S2013040013853);中国博士后科学基金面上项目(No.2012M521587);中国博士后科学基金特别资助项目(No.2014T70798)

摘　　要：目的探讨十溴联苯醚(BDE-209)暴露对人胚胎干细胞分化潜能的影响。方法分别将对数生长期未分化的人胚胎干细胞FY-h ES-10细胞暴露于含有终浓度为0(溶剂对照)、1、10和100 nmol/L BDE-209的培养基中培养96 h后,采用悬浮法培养拟胚体(embryoid body,EB)自发分化10 d,实时荧光定量PCR检测EB中OCT4、内胚层标志基因AFP、外胚层标志基因PAX6、中胚层标志基因SMA及氧化应激相关基因HIF1a、HIF2a和SOD1基因的表达,并测定SOD活性。结果与对照组比较,各剂量BDE-209暴露组FY-h ES-10细胞EB分化10 d OCT4、SMA、HIF1a和HIF2a表达水平均较高,而AFP、PAX6、SOD1表达水平均较低,差异有统计学意义(P<0.05)。且随着BDE-209暴露剂量的升高,FY-h ES-10细胞分化10 d EB中OCT4的表达水平均呈上升趋势,SOD1基因的表达水平呈下降趋势。同时BDE-209暴露后FY-h ES-10细胞分化10 d EB中SOD活性降低。结论 BDE-209可能通过影响早期胚胎的分化潜能从而产生发育毒性。Objective To study the effects of decabrominated biphenyl ether（ BDE-209） exposure on differentiation capacity of human embryonic stem cells. Methods Human embryonic stem cell line FY-h ES-10 cells were exposed to the concentrations of 0（ solvent control）,1,10 to 100 nmol/L BDE-209 for 96 h and then were differentiated into embryoid bodies（ EBs） in vitro. The RNA of EBs derived from FY-h ES-10 cells at Day10 was collected. OCT4,three-layer differentiation-related genes（ AFP,SMA and PAX6）and oxidative stress-related genes（ HIF1 a,HIF2a and SOD1） expression was detected by Q-PCR. The contents of SOD was measured by using kit. Results Compared with the solvent control group,the expression levels of OCT4,SMA,HIF1 a and HIF2 a in BDE-209 exposure groups were increased,the expression levels of AFP,PAX6 and SOD1 weredecreased,with statistically significant differences（ P〈0. 05）. With the increase of the BDE-209 dose,the expression levels of OCT4 showed an increasing trend while the expression levels of SOD1 and the activity of the SOD showed a decreasing trend.Conclusion BDE-209 may interfere with differentiation capacity of human embryonic stem cells resulting in developmental toxicity.

关 键 词：十溴联苯醚 胚胎干细胞 分化潜能 氧化应激 

分 类 号：R994.6[医药卫生—毒理学] Q786[医药卫生—药学]