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

PurposeCadmium (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, PKCα, and CaMKII gene expression is downregulated in the Cd-induced VBWD during early embryogenesis.MethodsAfter 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, PKCα, and CaMKII in the Cd-induced VBWD chick model.ResultsThe mRNA expression levels of Wnt11, PKCα, 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.ConclusionDownregulation of Wnt11, PKCα, and CaMKII gene expression during the narrow window of early embryogenesis may cause VBWD, interfering with cell movement and adhesion, disrupting Wnt/Ca2+ pathway.