Alterations in rat fetal morphology following abuse patterns of toluene exposure
Alterations in rat fetal morphology following abuse patterns of toluene exposure
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DOI：
10.1016/j.reprotox.2009.01.002
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发表时间：
2009-04-01
影响因子：
3.3
通讯作者：
Stefanski, Adrianne L.
中科院分区：
文献类型：
--
作者：
Bowen, Scott E.;Irtenkauf, Susan;Stefanski, Adrianne L.
甲苯是一种常被滥用的有机溶剂。吸入性滥用者越来越多的是处于最佳生育年龄段的女性。怀孕期间滥用溶剂的母亲所生的孩子可能会表现出“胎儿溶剂综合症”的特征，其中可能包括畸形特征。这项研究考察了孕期暴饮甲苯的滥用模式对胎鼠骨骼和软组织畸形、体重和身体大小的影响。怀孕的SD大鼠从妊娠第8天到GD20，每天两次，暴露在空气(0ppm)、8000ppm、12000ppm或16000ppm甲苯中30分钟。每窝动物的三分之二用于茜素红S染色进行骨骼检查，其余三分之一固定在Bouin‘s液中用于威尔逊软组织评估。暴露于所有水平的甲苯都会显著降低生长，包括胎盘重量、胎儿体重和头臀长度的减少。此外，还观察到许多肉眼形态异常，如手指短小或缺失以及四肢缺失。骨骼检查显示，由于各级甲苯暴露，四肢骨化显著减少。特殊的骨骼缺陷包括畸形的肩胛骨，缺失和多余的脊椎和肋骨，以及融合的手指。所有甲苯水平的软组织异常也被观察到，并且异常的数量随着剂量的增加而增加，包括隐睾症、腹部器官移位、胃肥大、膀胱扩张/发育不良和心脏发育延迟等。这些结果表明，产前暴露于典型的吸入剂滥用甲苯水平和模式的动物，骨骼和软组织异常的风险增加。(C)2009 Elsevier Inc.保留所有权利。
Toluene is a commonly abused organic solvent. Inhalant abusers are increasingly women in their prime childbearing years. Children born to mothers who abused solvents during pregnancy may exhibit characteristics of a "fetal solvent syndrome" which may include dysmorphic features. This study examined the teratological effects of an abuse pattern of binge toluene exposure during gestation on skeletal and soft tissue abnormalities, body weight, and body size in fetal rats. Pregnant Sprague-Dawley rats were exposed for 30 min, twice daily, from gestational day (GD) 8 through GD20 to either air (0 ppm), 8000 ppm, 12,000 ppm, or 16,000 ppm toluene. Two-thirds of each litter was prepared for skeletal examination using Alizarin Red S staining while the remaining third of each litter was fixed in Bouin's solution for Wilson's soft tissue evaluation. Exposure to toluene at all levels significantly reduced growth, including decreases in placental weight, fetal weight, and crown-rump length. In addition, numerous gross morphological anomalies were observed such as short or missing digits and missing limbs. Skeletal examination revealed that ossification of the extremities was significantly reduced as a result of toluene exposure at all levels. Specific skeletal defects included misshapen scapula, missing and supernumerary vertebrae and ribs, and fused digits. Soft tissue anomalies were also observed at all toluene levels and there was a dose-dependent increase in the number of anomalies which included cryptorchiclism, displaced abdominal organs, gastromegaly, distended/hypoplastic bladder, and delayed cardiac development, among others. These results indicate that animals exposed prenatally to levels and patterns of toluene typical of inhalant abuse are at increased risk for skeletal and soft tissue abnormalities. (C) 2009 Elsevier Inc. All rights reserved.