Downregulation of AP-2α Gene Expression in the Cadmium-Induced Ventral Body Wall Defect in the Chick Model

抄録

Purpose: Omphalocele is one of the most common ventral body wall defects in humans. In chick embryos, administration of the heavy metal cadmium (Cd) after 60-hour incubation induces the ventral body wall defect (VBWD), a similar event that manifests in human omphaloceles. We have previously reported that the earliest detectable histological changes in the Cd-induced chick model are observed 4 hours posttreatment. However, the exact mechanism by which Cd acts in early embryogenesis still remains unclear. The transcription factor AP-2α null mice has been shown to cause VBWD. We hypothesized that Cd-induced VBWD results from downregulation of AP-2α gene expression during the critical period of embryogenesis. Methods: Chick embryos were harvested 1 hour (1 H), 4 H and 8 H after treatment with cadmium and divided into control and Cd (n=8 at each time point) groups. Total mRNA extraction and real-time RT-PCR was performed to evaluate the mRNA expression levels of AP-2α in the Cd-induced VBWD. Differences between the two groups at each time point were analyzed statistically and statistical significance was accepted for differences where p<0.05. Results: The relative mRNA expression level of AP-2α at 4 H was significantly (p<0.05) decreased in the Cd group (1.84±2.72) compared to controls (4.08±1.36). However, the gene expression levels of AP-2α at 1 H and 8 H were not significantly different between the Cd and control groups. Conclusions: Our results provide evidence for the first time that the gene expression of AP-2α is downregulated 4 hours after treatment in the Cd-induced VBWD chick model. We speculate that the downregulation of AP-2α gene expression during this narrow window of embryogenesis may have caused VBWD.