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 expos ed to Adriamycin demonstrate a similar series of anomalies. It is the aim o f this study to characterize the spectrum of limb anomalies in this model. Female Sprague-Dawley rats (N = 18; 14 experimental and 4 control) were use d. After mating, pregnant animals received intraperitoneal injections of Ad riamycin (2 mg per kilogram) on days 6, 7, 8, and 9 of gestation. Fetuses w ere recovered on day 21 of gestation. Ten experimental litters (42 fetuses) and two control litters (18 fetuses) underwent skeletal staining with Aliz arin Red S stain. Four experimental litters (N = 18) and two control litter s (N = 17) underwent histological study including staining for vascular and neural structures. Upper limb anomalies were found in 45% of the experimen tal animals, all including either hypoplasia or bending of the radius. The ulna was involved in 37% of the affected limbs. There were no isolated ulna r deformities. There were no histological differences noted. The spectrum o f 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 a rise.