Congenital anomalies in mice induced by etretinate.

Abstract

We report on the experimental induction of anorectal malformations (ARM) and other internal and external malformations in mouse fetuses induced by maternal administration of etretinate, a long-acting vitamin A analogue. The teratogen was administered to pregnant mice between the 7th and 10th gestational days (E7 and E10). The mice of the control group were given pure sesame oil on E9. We examined survival rates, crown-rump length, and the incidence of internal and external malformations, with particular attention to ARM, in each group. All mice in the E8 group exhibited rectovesical fistula, hydronephrosis, and spina bifida. All males and females in the E9 group given 60 mg/kg of etretinate developed rectoprostatic urethral fistula and rectocloacal fistula, respectively. The E10 group, given 60 mg/kg of etretinate displayed cleft palate (63.6%), forelimb malformation (68.2%), and a short club-shaped tail (100%). The fetuses had more severe types of ARM when etretinate had been administered on an earlier gestational day. The E9 group is a useful model for anorectal malformation, whereas the E8 group is a model for hydronephrosis and spina bifida.