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Teratogenesis and gene targets of 17a-ethynylestradiol on embryonic development in zebrafish

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Author:: No author available

Journal Title:: ACTA PHARMACEUTICA SINICA

Issue:: 1

DOI:: No doi available

Key Word:: 17α-乙炔雌二醇;致畸作用;基因靶位;斑马鱼;胚胎发育;敏感期

Abstract：随着炔雌二醇临床适用范围的扩大和畜牧渔业中的滥用所导致的环境污染,使得建立准确、简便、快速的体内检测方法和开展对雌二醇的胚胎发育毒理研究愈显重要.本文以17α-乙炔雌二醇(17α-ethynylestradiol,EE2)为代表化合物,利用模式动物斑马鱼研究了EE2的致畸性、靶组织和靶基因及其对胚胎心律的影响.结果表明,EE2的半数致畸浓度(TC50)为0.8 μg·ml-1,半数致死浓度(LD50)为3.3μg·mL-1;其致畸靶位涉及脑和眼、心、肌肉、骨骼、色素和内脏.EE2可导致胚胎心率异常.胚胎对EE2敏感期主要在器官形成期之前,且具有时间积累效应.RT-PCR结果显示,EE2可抑制头部发育基因如boz,促进躯干和尾部发育的基因如ntl、spt和成形素shh基因,干扰多功能的Nodal信号基因cyc、sqt和oep.本研究利用斑马鱼建立了快速、有效体内检测炔雌二醇类化合物胚胎毒性的方法.

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