Patterns of radial dysmorphology with the VACTERL association in the adriamycin-exposed prenatal rat

The VACTERL association is an acronym for a constellation of abnormalities affecting the spinal column, anus, heart, trachea, esophagus, kidneys, and limbs that are seen in newborns. It has been shown that prenatal rats exposed to Adriamycin demonstrate a similar series of anomalies. It is the aim of this study to characterize the spectrum of limb anomalies in this model. Female Sprague-Dawley rats (N = 18; 14 experimental and 4 control) were used. After mating, pregnant animals received intraperitoneal injections of Adriamycin (2 mg per kilogram) on days 6, 7, 8, and 9 of gestation. Fetuses were recovered on day 21 of gestation. Ten experimental litters (42 fetuses) and two control litters (18 fetuses) underwent skeletal staining with Alizarin Red S stain. Four experimental litters (N = 18) and two control litters (N = 17) underwent histological study including staining for vascular and neural structures. Upper limb anomalies were found in 45% of the experimental animals, all including either hypoplasia or bending of the radius. The ulna was involved in 37% of the affected limbs. There were no isolated ulnar deformities. There were no histological differences noted. The spectrum of upper limb anomalies seen in the Adriamycin-exposed prenatal rat closely approximates, in incidence and morphology, the upper limb deformities seen with the VACTERL association in children. It is a reliable model for use in additional studies of the embryological mechanism by which these defects arise.