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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 study the developmental toxicity of all-trans retinoic acid (atRA) and its possible mechanism. In this study, we investigated the effect of atRA on the growth and development of mouse embryos by using whole-embryo culture in vitro. Methods The pregnant embryos were transplanted in whole embryo medium with the final concentrations of atRA of 0, 0.01, 0.1, 0.2, 0.4, 1.0 and 10.0 μmol / L at embryonic day 8 and culture for 48 hours. The effects of atRA on embryonic development and organ morphology The impact of differentiation. Results atRA could affect the growth and development of mouse embryos in vitro and showed a dose-response relationship. AtRA at 0.1 μmol / L significantly affected the diameter of yolk sac, cranial buttocks, forebrain, midbrain, auditory system, visual system, heart , Body position and forelimb buds and other indicators, compared with the control group, the difference was significant (P <0.05); ≥ 0.20μmol / L group, yolk sac volume decreased, surface shrinkage, decreased blood vessels and decreased differentiation, nervous system, The deformities of heart, arch and craniofacial were observed. The morphological changes of all organs were significantly lower than those of the control group (P <0.05). Conclusions AtRA has teratogenicity and embryotoxicity, which may cause the developmental deformities of various organs such as the nervous system, heart, bicept and craniofacial during organogenesis.