维甲酸诱导小鼠神经管畸形的剂量依赖性和时间特异性

Retinoic acid induced neural tube defects in C57 mice in a dose-dependent and time-specific way

目的探索不同的维甲酸(retinoic acid,RA)剂量对小鼠神经系统发育的影响以及在特异时间点作用于小鼠胚胎时对神经管闭合的影响。方法采用C57孕鼠于GD7.5分别腹部注射5mg/kg,7.5mg/kg,20mg/kg RA,于GD10.5腹部注射20mg/kg RA,观察胎鼠表型并称量胎鼠重量,胎脑重量,测量眼距和顶距(前囟到鼠喙的距离)。结果 GD7.5腹部注射5mg/kg RA的胎鼠出现无眼畸形,7.5mg/kg的胎鼠出现脑膨出,20mg/kg的吸收胎率为100%,GD10.5腹部注射20mg/kg RA的胎鼠前肢短小其中,GD7.5给予7.5mg/kg RA处理后的胎鼠脑重显著低于正常组和其他实验组;GD7.5时给予7.5mg/kg RA处理组及GD10.5时20mg/kg RA处理组的胎鼠重量显著低于正常组;GD7.5时5mg/kg RA处理组的胎鼠顶距低于正常组。结论在胚胎发育的不同时期暴露于过量的RA会影响不同器官的发育,而且RA对颅面畸形的影响呈剂量依赖性。

Objective： To explore the effects of different doses of RA （retinoic acid） on the developing nervous system of mice and the impact of different time points of RA usage on mouse embryonic neural tube closure. Methods： C57 pregnant mice was treated with RA at GD7.5 in doses of 5mg/kg, 7.5mg/kg, 20mg/kg through abdomen injection, at GD10.5 in a dose of 20mg/ kg. Observing the fetal phenotype, weighing fetal weight and fetal brain weight, measuring eyes distance and vertex distance （the distance between bregma and mouth） . Results.- The group of GD7.5 5mg/kg appear anophthalmos, the group of GD7.5 7.Smg/kg appear encephalocele. The group of GD7.5 20mg/kg were absorbed in 100% rate, while the group of GD10.5 20mg/kg shows short forelimbs phenotype. Fetal brain weight of GD7.5 7.5mg/kg was significantly lower than the normal group and other groups, fetal weight ofGD7.5 7.5mg/kg and GD10.5 20mg/kg were significantly lower than the normal group, the vertex distance of GD7.5 5mg/ kg was lower than normal fetuses. Conclusion： In different stages of embryonic development, excess RA exposure can affect the development of different organs, and the RA induced craniofacial deformities appear in a dose-dependent manner.