全反式视黄酸对小鼠胚胎发育毒性的体外实验研究  

Effects of all-trans retinoic acid on mouse embryonic development : An in vitro study

作　　者：韩静[1] 张大超 肖颖[1] 张召锋[1] 柳鹏[1] 李丽[1] 余增丽[1] 李勇[1] 

机构地区：[1]北京大学公共卫生学院营养与食品卫生学系 [2]北京怡生安康信息咨询有限公司

出　　处：《中国生育健康杂志》2005年第4期217-220,共4页Chinese Journal of Reproductive Health

基　　金：国家"973"项目(2001CB510305);国家自然科学基金(30371208);中国博士后基金(2004035025)

摘　　要：目的为研究全反式视黄酸(atRA)的发育毒性及其可能的作用机制,本研究采用植入后体外全胚胎培养方法研究atRA对小鼠胚胎生长发育的影响。方法孕8.5日龄小鼠胚胎移植于atRA终浓度为0、0.01、0.1、0.2、0.4、1.0、10.0μmol/L的全胚胎培养基中,体外连续培养48h,观察atRA对胚胎发育和器官形态分化的影响。结果atRA可影响小鼠胚胎在体外的生长发育,并呈现剂量-效应关系;0.1μmol/L组,atRA明显影响卵黄囊直径、颅臀长、前脑、中脑、听觉系统、视觉系统、心脏、体位和前肢芽等指标,与对照组比较,差异有显著性(P<0.05);≥0.20μmol/L组,卵黄囊体积减小、表面皱缩、血管减少及分化程度降低,神经系统、心脏、腮弓和颅面等多种器官出现畸形,所有器官形态分化指标均显著低于对照组(P<0.05)。结论atRA有致畸性和胚胎毒性,在器官形成期可以引起神经系统、心脏、腮弓和颅面等多种器官的发育畸形。Objective To investigate the developmental toxicity of all-trans retinoic acid （atRA） and its possible mechanism, the post-implantation whole embryo culture （WEC） was used. Methods Early somite stage （GD 8.5） mouse embryos were explanted and cultured in rat serum medium （immediately centrifugal serum, ICS） with atRA （0, 0. 01, 0. 1, 0. 2, 0. 4, 1.0, 10. 0μmol/L） for 48 h to evaluate the embryo development and morphological differentiation. Results atRA did cause damages to embryonic development in a significant dose-response pattern. 0.01μM group caused no significant differences to embryonic development and organ morphological scores compared with the non-atRA treated controls （P〉0. 05）. 0. 1μmol/L group led to the significant decrease of scores of visceral yolk sac （VYS） diameter, crown rump length, forebrain, midbrain, auditory system, visual system, heart, trunk turning, forelimb bud （P〈0. 05）.≥0.20 μmol/L group resulted in significant inhibiting effects on VYS （including reduced VYS diameter, shriveled surface, small or defective VYS vessels）. Malformations were observed in organ systems that involved central nervous system, cardiac, branchial arch and craniofacies. Developmental morphological score were apparent with increased atRA （P〈0. 05）. Conclusion atRA could result in embryonic development retardation and teratogenic toxicity, causing malformations in different organs during organ forming periods. The damage on structure and function of VYS might be part of teratogenic mechanisms.

关 键 词：全反式视黄酸 小鼠 胚胎发育 毒性 体外实验 atRA 发育毒性 

分 类 号：R114[医药卫生—卫生毒理学]