Jarvis B L, Johnston M C, Sulik K K
Department of Otolaryngology-Head and Neck Surgery, West Virginia University, Morgantown 26506.
Otolaryngol Head Neck Surg. 1990 Apr;102(4):391-401. doi: 10.1177/019459989010200414.
Isotretinoin (Accutane), a widely used dermatologic drug, produces severe congenital malformations when used during pregnancy. The isotretinoin teratogen syndrome consists of multiple cardiovascular and craniofacial anomalies, most commonly involving the external ear. This study examined the pathogenesis of isotretinoin teratogenicity in a mouse model, using microdissection and histologic examination of fetal mouse ears after treatment with the drug at various stages of embryonic development. In this study, earlier treatment times frequently produced microtia similar to that seen in affected infants, as well as recognizable patterns of temporal bone and ossicular abnormalities; exposure at a later developmental stage resulted in facial tags with less severely affected ears. Possible teratogenic mechanisms of isotretinoin are discussed. Suitability of the mouse model for studying human congenital craniofacial malformations, such as Goldenhar's and Treacher Collins Syndrome, is also explored.
异维甲酸（泰尔丝）是一种广泛使用的皮肤科药物，孕期使用会导致严重的先天性畸形。异维甲酸致畸综合征包括多种心血管和颅面异常，最常见的是外耳受累。本研究在小鼠模型中研究异维甲酸致畸作用的发病机制，在胚胎发育的不同阶段用该药物处理后，对胎鼠耳朵进行显微解剖和组织学检查。在本研究中，较早的治疗时间常常产生与受影响婴儿相似的小耳畸形，以及颞骨和听骨异常的可识别模式；在发育后期暴露会导致面部赘生物，耳朵受影响程度较轻。本文讨论了异维甲酸可能的致畸机制。还探讨了该小鼠模型用于研究人类先天性颅面畸形（如Goldenhar综合征和特雷彻·柯林斯综合征）的适用性。
