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Teratologic effects of Bis-diamine on cardiovascular development in rat embryo : in vivo and in vitro analysis

双二胺对大鼠胚胎心血管发育的致畸作用：体内和体外分析

基本信息

批准号：
09670800
负责人：
NAKAGAWA Masao
金额：
$ 1.54万
依托单位：
Shiga University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670800/
关键词：
confocal laser scanning micro-scope aortic arch anomaly bis-diamine whole embryo culture elongated outflow tract pericardial defect enlarged ventricle delayed neural tube closure WKY NCrjラット耳原基位置異常上顎突起過形成

项目摘要

Bis-diamine administration to pregnant rats induces conotruncal anomalies.To know teratologic effects of bis-diamine depending on the developmental stage, we examined neonates and embryos from Wister mother rats to which a single dose of 200 mg his-diamine was administered at 10, 11, or 12 days of gestation (group 1, 2, and 3, respectively). The neonates from group 1 (n 86) had aortjc arch anomalies in 100 %, and those from group 2 (n = 95) and 3 (n = 108) had aortic arch anomalies and truncus arteriosus communis in 92.8%, and aortic arch anomalies and tetralogy of Fallot in 45.4%, respectively. In order to examine the early morphological effects of bis-diamine, we cultured four embryos from each group for 24 hours following the procedures described by Cockroft and New (1978). The embryos from group 1 showed delayed closure of the neural tube and immature cardiac looping with undifferentiated third, fourth, and sixth Nortek arches. Immunohistological study using anti-N-CAM antibody revealed that N-CAM positive cells were sparsely distributed around the neural tube. The embryos from group 2 had an enlarged and dilated ventricle and winding and elongate outflow tract in which regurgitant blood flow was observed, whereas none in controls. Furthermore, two of the embryos had a partial pericardial defect. A continuous N-CAM immunopositive chain from the neural tube to the heart was clearly seen, though thin when compared with controls. No morphological and circulatory difference was seen between embryos from group 3 and controls.These results suggested that bis-diamine may disturb normal development and migration of cardiac neural crest or mesenchymal cells to induce various cardiovascular anomalies depending on the developmental stage.

双二胺给药妊娠大鼠conotrumal aberrations.To了解双二胺的致畸作用取决于发育阶段，我们检查了新生儿和胚胎从Wister母鼠，单剂量的200毫克组氨酸二胺，在10，11，或12天的妊娠（组1，2，和3，分别）。第1组86例，主动脉弓畸形100%，第2组95例，第3组108例，主动脉弓畸形合并总动脉干92.8%，主动脉弓畸形合并法洛四联症45.4%。为了检查双二胺的早期形态学效应，我们按照Cockroft和New（1978）描述的程序将每组的4个胚胎培养24小时。第1组的胚胎表现出神经管延迟闭合和未成熟的心脏循环，具有未分化的第三、第四和第六Nortek弓。免疫组化显示N-CAM阳性细胞在神经管周围呈稀疏分布。第2组的胚胎有一个扩大和扩张的心室和弯曲和延长的流出道，其中观察到反流性血流，而在对照组中没有。此外，其中两个胚胎有部分心包缺陷。从神经管到心脏的连续N-CAM免疫阳性链清晰可见，但与对照组相比较薄。第3组胚胎与对照组胚胎在形态学和循环方面没有观察到差异。这些结果表明，双二胺可能会干扰心脏神经嵴或间充质细胞的正常发育和迁移，从而诱发各种心血管异常，具体取决于发育阶段。