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espanolResumen: Objetivo: El acido retinoico es un metabolito activo de la vitamina A que administrado en grandes cantidades tiene efecto teratogeno sobre la embriogenesis de los mamiferos. Hemos investigado los efectos de la exposicion temprana de embriones de rata sobre las estructuras craneofaciales. Diseno: Cuarenta y cinco ratas Sprague-Dawley gestantes fueron tratadas con 125 mg/kg de acido all-trans-retinoico el dia 10 de gestacion. Las 20 ratas controles fueron tratadas con aceite. Los fetos de ambos grupos se extrajeron el dia antes de llegar a termino y fueron sometidos a un estudio morfologico y otro estudio morfometrico, analizando las malformaciones craneofaciales. Resultados: Ninguno de los fetos controles presento malformaciones. El 100% de los embriones tratados con retinoico presentaron defectos craneofaciales, incluyendo fisuras faciales, exoftalmos, malformaciones e insercion baja de los pabellones auriculares, apendices faciales y anomalias nasales. El analisis morfometrico revelo un incremento de la distancia entre los poros nasales (p Conclusiones: Tanto el estudio morfologico como el estudio morfometrico confirman la hipotesis segun la cual el acido retinoico altera el desarrollo craneofacial cuando se administra durante un momento critico del desarrollo embrionario. Una alteracion en la migracion de las celulas de la cresta neural craneal podria ser la razon que explicaria estas anomalias. EnglishAbstract: Objective: Retinoic acid is an active metabolite of Vitamin A that is teratogenic when present in excess during mammalian embriogenesis. We have investigated the effects of early exposure of rat embryos to retinoic acid on craniofacial structures. Design: Treatment of 45 pregnant Sprague-Dawley rats with 125mg./Kg all-trans-retinoic acid on pregnancy day 10 was performed. Twenty controls were treated only with oil. The fetuses were recovered the day before term, and both morphologic and morphometric analyses of the craniofacial structures were performed. Results: None of the control fetuses had malformations. Craniofacial defects were observed in 100% of the retinoic embryos including facial clefts, proptosis, abnormalities and inferior placement of the pinnae, skin tags, and nasal anomalies. Morphometric analyses revealed an increased distance between nasal pores (p Conclusions: Morphologic and morphometric studies confirm the hypothesis that retinoic acid disturbs normal craniofacial development when administered during a critical period. Hindrance of migration of the cranial neural crest cells may be a main reason to explain these events.

Estudio morfométrico de las malformaciones craneofaciales experimentales inducidas por ácido retinoico