Congenital diaphragmatic hernia after exposure to a triple retinoic acid antagonist during pregnancy

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Abstract

Aim

To establish a mouse model for the study of congenital defects, using exposure of pregnant females to the teratogen BMS-189453, a multiple retinoic acid competitive antagonist.

Aim

We found not less than 60% of fetuses had transposition of the great arteries and l5% had other congenital heart defects such as double outlet right ventricle, tetralogy of Fallot, truncus and right aortic arch. Newborns exposed in utero to BMS-189453 were affected by thymus aplasia or hypoplasia, and severe congenital anomalies of the central nervous system due to neural tube defects. An anterior rotation of the right lung was also frequently present in our model. We also report a case of murine congenital diaphragmatic hernia associated with thymic aplasia and transposition of the great arteries.

Conclusion

These findings support the hypothesis that the combination of diaphragmatic hernia and congenital heart defects may be related to an alteration of the retinoic acid signaling pathways.

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