Effects of cadmium on formation of the ventral body wall in chick embryos and their prevention by zinc pretreatment

Abstract

Cadmium (Cd) is an established experimental teratogen whose effects can be reversed by pretreatment with zinc. Mesodermal development is a frequently reported target for Cd teratogenicity. The aim of this study was to examine the mechanisms of Cd induced body wall defects in chick embryos. Chick embryos in shell-less culture were treated with 50 microl of cadmium acetate (8.9 x 10(-5) M Cd(2+)) at 60-hr incubation (H.-H. stages 16-17). Controls received equimolar sodium acetate. Other embryos were treated with various concentrations of zinc acetate and then with Cd or NaAc 1 hrs later. Development was evaluated 48 hrs later. Resin-embedded 1-microm sections were examined at earlier stages. Cd caused embryolethality (35%), ventral body wall defect with malpositioned lower limbs (40%), and weight reduction in survivors. After 4-hr treatment with Cd, breakdown of junctions between peridermal cells with rounding up and desquamation occurred. Shape changes were also seen in the basal layer of the ectoderm. At 4 hr, cell death was evident in lateral plate mesoderm, somites, and neuroepithelium; the lateral plate mesoderm began to grow dorsally, carrying the attached limb buds with it. Zn pretreatment protected against the lethal, teratogenic, and growth-retarding effects of Cd, as well as ectodermal changes and cell death. Cd disrupts peridermal cell adhesion and induces cell death in the mesoderm. This may result in abnormal growth of lateral plate mesoderm and in a body wall defect. Zn pretreatment prevents both the gross teratogenic effects and the cellular changes, most likely by competition with Cd.