Disruption of noncanonical Wnt/CA2+ pathway in the cadmium-induced omphalocele in the chick model

Purpose: Cadmium (Cd) has been found to cause ventral body wall defects (VBWDs) in the chick embryo similar to human omphalocele. The earliest detectable histologic changes in Cd-induced VBWD chick model have been observed 4 hours posttreatment. The exact mechanism by which Cd acts in the early embryogenesis remains unclear. Wnt proteins play a key role during embryogenesis, and altered Wnt signaling has been linked to developmental defects. Noncanonical Wnt/Ca2+ pathway has been implicated in regulating embryogenesis by controlling cell movement and adhesion. Wnt11 can activate protein kinase C (PKC) and calcium/calmodulin-dependent kinase II (CaMKII) in the Wnt/Ca2+ pathway. We hypothesized that the Wnt11, PKC alpha, and CaMKII gene expression is downregulated in the Cd-induced VBWD during early embryogenesis. Methods: After 60 hours of incubation, chick embryos were harvested 1 hour (1H), 4H, and 8H after treatment of saline or cadmium and divided into 2 groups: control and Cd (n = 8 at each time-point, respectively). Real-time polymerase chain reaction was performed to evaluate the messenger RNA (mRNA) expression of Wnt11, PKC alpha, and CaMKII in the Cd-induced VBWD chick model. Results: The mRNA expression levels of Wnt11, PKC alpha, and CaMKII were significantly decreased at 1H in Cd group compared to controls (P < .05). However, there were no significant differences in the other time-points. Conclusion: Downregulation of Wnt11, PKC alpha, and CaMKII gene expression during the narrow window of early embryogenesis may cause VBWD, interfering with cell movement and adhesion, disrupting Wnt/Ca2+ pathway. (C) 2010 Elsevier Inc. All rights reserved.