吡虫啉暴露致早期胚胎心管和神经管发育异常暨南大学高麟芮.DOCVIP

吡虫啉暴露致早期胚胎心管和神经管 发育异常 暨南大学 高麟芮，张诗瑶，钟山 （暨南大学再生医学重点实验室，广东省 广州 510632） 作者简介：高麟芮（1995-）、女，内蒙古，临床医学，2013级，主要从事组织胚胎学等研究。 张诗瑶（1995-）、女，辽宁，临床医学，2013级，主要从事组织胚胎学等研究 钟山（1994-）、男，内蒙古，临床医学，2013级，主要从事组织胚胎学等研究 （Journal Of Agricultural And Food Chemistry, 2016; Toxicological Sciences, 2016; Molecular Neurobiology, 2017） 王广 副教授，杨雪松 教授 中文摘要：作为新烟碱类农药，吡虫啉被广泛用于消灭农业中的害虫，然而吡虫啉暴露是否会影响心脏和神经发生并不可知。本研究利用鸡胚模型，探究吡虫啉暴露对胚胎发育的影响。将HH0鸡胚暴露于吡虫啉会导致心管畸形。研究显示GATA4，Nkx2.5和BMP4的下调以及Wnt3a的上调会导致心肌细胞异常分化；吡虫啉干扰EMT过程，限制心脏祖细胞向第一生心区迁移。另外，NF/Tuj1荧光结果表明吡虫啉会导致胚胎神经管缺陷和神经元发育不良。吡虫啉使神经管顶端的F-actin蛋白被抑制，且神经管的背侧和腹侧的BMP4和Shh的表达也降低。实验数据和生物信息学分析表明，吡虫啉暴露可增加胚胎心管、神经管缺陷和神经发育不良的风险。 英文摘要：As a neonicotinoid pesticide, imidacloprid is widely used to control insects in agriculture. However, it is not known whether imidacloprid exposure negatively affects cardiogenesis and neurogenesis during embryonic development. In this study, using a chick embryo model, we investigated the effects of imidacloprid exposure on embryo development. Exposing HH0 chick embryos to imidacloprid caused heart tube malfomation. The data reveals that down-regulation of GATA4, Nkx2.5 and BMP4 and up-regulation of Wnt3a led to aberrant cardiomyocyte differentiation. Imidacloprid interfered with EMT process and restricted the cell migration of cardiac progenitors to primary heart field. Also, imidacloprid caused neural tube defects and neuronal differentiation dysplasia as determined by NF/Tuj1 labeling. We found that F-actin accumulation on the apical side of the neural tube was suppressed, and the expression of BMP4 and Shh on the dorsal and ventral sides of the neural tubes, respectively, were also reduced. The experimental evidence and bioinformatics analysis suggested that imidacloprid could increase the risk of heart tube malformation, neural tube defects and neural dysplasia. 关键词：鸡胚；吡虫啉；心管不融合；神经管缺陷 研究背景 器官发生需要将多种细胞精确地布控，从而形成正常器官特定的三维结构。在胚胎器官发育期间组织融合是一个必须的过程，例如视杯、腭、心脏、神经管、眼睑和体壁组织融合 ADDIN EN.CITE ADDIN EN.CITE.DATA [ HYPERLINK \l _ENREF_1 \o Ray, 20