Malformations in offspring of diabetic rats: Morphometric analysis of neural crest-derived organs and effects of maternal vitamin E treatment

Background: We have previously reported on a malformation-prone Sprague-Daw ley rat substrain (U), which presents a high frequency of micrognathia in t he offspring of diabetic mothers. This malformation is related to impaired development of the cranial neural crest cells (NCC); the defect may be prev ented by antioxidative treatment of the mother. Methods: We have therefore investigated whether fetuses of diabetic rats di splay other malformations associated with altered cranial NCC development a nd whether maternal vitamin E supplementation may affect such malformations . Results: Fetuses of diabetic rats showed low-set external ears, severely ma lformed Meckel's cartilage, small thyroid and thymus, and absence of parath yroid glands. Cardiac anomalies were frequently observed, including rightwa rd displacement of the aorta, double outlet right ventricle (DORV), persist ent truncus arteriosus (PTA) combined with ventricular septal defects due t o a malaligned outlet septum. The malformations in the outflow tract includ ed abnormalities of the great arteries; right-sided aortic arch/descending aorta, and double aortic arches. These defects tended to occur together wit hin individual fetuses. Maternal dietary treatment with 2% vitamin E marked ly reduced the severity of the malformations. Conclusions: The phenotypic appearance of these defects is strikingly simil ar to the DiGeorge anomaly in humans, which has been found in children of d iabetic mothers together with an overrepresentation of PTA and DORV. The ma lformations associated with defective NCC development in the offspring of d iabetic U rats show several morphological similarities to those in humans; hence the teratogenic mechanisms may be similar and accessible for study. ( C) 2000 Wiley-Liss, Inc.