The classification and development of cadmium-induced limb defects in mice



The aim of this study was to investigate the teratogenic action of cadmium (Cd) on the developing mouse limb. Pregnant mice (C57BL/6J strain) received an injection of 4mg/kg CdCl2 on day 8,9 or 10 of gestation. These animals and saline injected controls were sacrificed either on the day before birth or at various times up to 72 hours after injection.

Limb defects occurred after treatment on each day, the most severe occurring after early treatment. The forelimb deformities were predominantly postaxial reduction while hindlimb defects were preaxial and involved reduction, hypertrophy, syndactyly and polydactyly. The most severe limb reductions were associated with abnormalities of the spinal cord.

Eight to 12 hours after maternal injection with Cd on day 9, the cells of the neural tube and forelimb buds from affected embryos showed large numbers of cytolysosomes. In severely affected limbs both ectodermal and mesodermal cells were involved. In less affected limbs the cytolysosomes were restricted to the mesodermal cells immediately deep to the ectoderm. Right and left limbs appeared to be equally involved with damage extending throughout the craniocaudal length of the limb. By 24 hours most of the cytolysosomes had disappeared. In the neural tube they were replaced by large amounts of cell debris while in the limbs a range of morphology was seen. In the least developed limbs there were still some inclusions but also extracellular debris, while in other, more developed limbs, there was little or no sign of damage. By 48 and 72 hours after treatment all signs of cellular damage had disappeared. The wall of the neural tube however, was frequently thin and sometimes discontinuous while the limbs showed abnormalities in shape such as flattening of the postaxial margin and shortening of the anterior-posterior axis.