Emmanouil-Nikoloussi E N, Goret-Nicaise M, Foroglou C H, Katsarma E, Dhem A, Dourov N, Persaud T V, Thliveris J A
Laboratory of Histology-Embryology, Faculty of Medicine, Aristotelian University of Thessaloniki, Greece.
Exp Toxicol Pathol. 2000 Oct;52(5):445-53. doi: 10.1016/s0940-2993(00)80080-9.
Exogenous retinoic acid has been found to be teratogenic in animals and man. Craniofacial defects induced by retinoic acid have stimulated considerable research interest. The present report deals with scanning electron microscopical observations of the craniofacial region concurrent with histological examination of craniofacial dysmorphism induced in rat embryos following maternal treatment treated with varying dosages of all-trans-retinoic acid (tretinoin). Two groups of pregnant rats were treated with rat embryos exposed to retinoic acid suspended in corn oil (100 mg/kg b.w. on gestational day 11.5 and 50 mg/kg b.w. on gestational day 10, 11 and 12 respectively). A third group was treated with corn oil (vehicle) while a fourth group remained untreated. A wide spectrum of congenital abnormalities, including exophthalmos, microphthalmia and anophthalmia, maxillo-mandibular dysostosis, micrognathia of both maxilla and mandible, cleft palate, subdevelopment of ear lobe, preauricular tags and macroglossia, were observed in the offspring of retinoic acid treated animals. The abnormalities were both time and dosage dependent, and characteristic of Treacher Collins syndrome when retinoic-acid was administered on gestational day 11.5. In contrast, when retinoic acid was administered were on gestational days 10-12, the defects were similar to those seen in the first and second pharyngeal arch syndrome, as well as in the oculo-auriculo-vertebral spectrum. Whereas our data support the hypothesis that all-trans retinoic-acid disturbs growth and differentiation of several embryonic cell types essential for normal craniofacial development, its mechanism of action remains unclear.
外源性视黄酸已被发现在动物和人类中具有致畸性。视黄酸诱导的颅面缺陷引发了大量的研究兴趣。本报告涉及对颅面部区域的扫描电子显微镜观察，并同时对母体经不同剂量全反式视黄酸（维甲酸）处理后大鼠胚胎中诱导的颅面畸形进行组织学检查。两组怀孕大鼠用悬浮于玉米油中的视黄酸处理其胚胎（分别在妊娠第11.5天给予100mg/kg体重，在妊娠第10、11和12天给予50mg/kg体重）。第三组用玉米油（赋形剂）处理，而第四组未处理。在视黄酸处理动物的后代中观察到了广泛的先天性异常，包括眼球突出、小眼症和无眼症、上颌-下颌骨发育不全、上颌和下颌均小颌畸形、腭裂、耳垂发育不全、耳前赘生物和巨舌症。这些异常与时间和剂量相关，当在妊娠第11.5天给予视黄酸时具有特雷彻·柯林斯综合征的特征。相比之下，当在妊娠第10 - 12天给予视黄酸时，缺陷类似于在第一和第二鳃弓综合征以及眼-耳-脊椎谱系中所见的缺陷。虽然我们的数据支持全反式视黄酸扰乱正常颅面发育所必需的几种胚胎细胞类型的生长和分化这一假说，但其作用机制仍不清楚。
