Fetal ear malformations induced by maternal ingestion of thalidomide in the bonnet Monkey (Macaca radiata)

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Abstract
Gross malformations of the external, middle, and internal ear were seen in fetal monkeys following maternal ingestion of thalidomide. Twenty‐five pregnant bonnet monkeys (Macaca radiata) were each given a single oral dose of 10 mg/kg of thalidomide on day 24, 25, 26, 27, 28, or 29, or 30 mg/kg on day 25 or 28 of gestation. (Day of mating is assumed to be day zero of pregnancy.) The skeletons, processed and stained with Alizarin Red S, were examined for changes in configuration and/or ossification of the ossicles and temporal bones. Bilateral temporal bones of one case, treated on day 24, were sectioned at 10 μm and examined histologically. Twelve fetuses collected at 70 ± 3 days of gestation showed no gross ear defects, while 10 out of 13 fetuses collected at 100 ± 3 days of gestation had structural anomalies similar to those observed in humans. All malformations were severe in fetuses treated on day 24 of gestation and lessened in degree of severity with treatments on days 25–28. Fetuses treated on day 29 were normal. External ear anomalies included microtia with meatal atresia or stenosis, and varying degrees of auricular hypoplasia. Defects of the middle ear were predominantly hypoplasia of malleus, incus, and tympanic ring. Fused ossicles and cochlear and vestibular window abnormalities were only seen in animals treated on day 24. The internal ear exhibited petrosal hypoplasia and delayed ossification of the lateral aspect of the lateral and posterior semicircular canals. Cochlear, vestibular, semicircular, and transcapsular canal defects were confirmed histologically in one case.