Cipollone Daria, Amati Francesca, Carsetti Rita, Placidi Silvia, Biancolella Michela, D'Amati Giulia, Novelli Giuseppe, Siracusa Gregorio, Marino Bruno
Department of Public Health and Cell Biology, University of Rome Tor Vergata, 00173 Rome, Italy.
Cardiovasc Pathol. 2006 Jul-Aug;15(4):194-202. doi: 10.1016/j.carpath.2006.04.004.
The morphogenetic mechanisms that are responsible for the transposition of the great arteries are still largely unknown, mainly because this malformation is very difficult to experimentally reproduce. The aim of the present study was to test the effect of BMS-189453, a retinoic acid antagonist, on murine heart morphogenesis.
We administered this drug at 5 mg/kg body weight (twice, at a 12-h interval) to pregnant mice on 6.25/6.75 days postcoitum (dpc) (Group A), 6.75/7.25 dpc (Group B), 7.25/7.75 dpc (Group C), 7.75/8.25 dpc (Group D), or 8.25/8.75 dpc (Group E). At birth, the anatomical features of fetuses were evaluated by stereomicroscopic examination.
In Group A (18 fetuses), cardiovascular anatomy was normal in 10 (56%) cases, and 8 (44%) fetuses presented with transposition of the great arteries. In Group B, no fetuses were obtained. In Group C (78 fetuses), cardiovascular anatomy was normal in 19 (24%) cases, while 59 (76%) mice presented with various types of cardiac defects, including 48 transpositions of the great arteries (61%). In Group D (80 fetuses), cardiac defects were seen in 22 (27%) mice: 14 of these (17%) were transpositions of the great arteries. In Group E (72 fetuses), cardiovascular anatomy was normal in all cases. Of 248 fetuses analyzed, 87% presented with thymic aplasia or hypoplasia, and 20% presented with meroanencephalia and/or rachischisis.
Transposition of the great arteries can be consistently reproduced in mice by administration of a retinoic acid competitive antagonist on 7.5 dpc.
导致大动脉转位的形态发生机制在很大程度上仍不清楚，主要是因为这种畸形很难通过实验重现。本研究的目的是测试视黄酸拮抗剂BMS - 189453对小鼠心脏形态发生的影响。
我们在妊娠第6.25/6.75天（A组）、6.75/7.25天（B组）、7.25/7.75天（C组）、7.75/8.25天（D组）或8.25/8.75天（E组）给怀孕小鼠按5mg/kg体重给药（两次，间隔12小时）。出生时，通过体视显微镜检查评估胎儿的解剖特征。
A组（18只胎儿）中，10例（56%）心血管解剖结构正常，8例（44%）胎儿出现大动脉转位。B组未获得胎儿。C组（78只胎儿）中，19例（24%）心血管解剖结构正常，而59只（76%）小鼠出现各种类型的心脏缺陷，包括48例大动脉转位（61%）。D组（80只胎儿）中，22只（27%）小鼠出现心脏缺陷：其中14只（17%）为大动脉转位。E组（72只胎儿）中，所有病例心血管解剖结构均正常。在分析的248只胎儿中，87%出现胸腺发育不全或发育不良，20%出现半叶无脑畸形和/或脊柱裂。
在妊娠第7.5天给小鼠施用视黄酸竞争性拮抗剂可一致地重现大动脉转位。
