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

Background: Cadmium (Cd) is an established experimental teratogen whose eff ects can be reversed by pretreatment with zinc. Mesodermal development is a frequently reported target for Cd teratogenicity. The aim of this study wa s to examine the mechanisms of Cd induced body wall defects in chick embryo s. Methods: Chick embryos in shell-less culture were treated with 50 mul of ca dmium acetate (8.9 x 10(-5) M Cd2+) at 60-hr incubation (H.-H. stages 16-17 ). Controls received equimolar sodium acetate. Other embryos were treated w ith various concentrations of zinc acetate and then with Cd or NaAc 1 hrs l ater. Development was evaluated 48 hrs later. Resin-embedded 1-mum sections were examined at earlier stages. Results: Cd caused embryolethality (35%), ventral body wall defect with mal positioned lower limbs (40%), and weight reduction in survivors. After 4-hr treatment with Cd, breakdown of junctions between peridermal cells with ro unding up and desquamation occurred. Shape changes were also seen in the ba sal layer of the ectoderm. At 4 hr, cell death was evident in lateral plate mesoderm, somites, and neuroepithelium; the lateral plate mesoderm began t o grow dorsally, carrying the attached limb buds with it, Zn pretreatment p rotected against the lethal, teratogenic, and growth-retarding effects of C d, as well as ectodermal changes and cell death. Conclusions: 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 teratog enic effects and the cellular changes, most likely by competition with Cd. (C) 2001 Wiley-Liss, Inc.