The SOD1 mimetic, tempol, abolishes high glucose-suppressed Wnt signaling, and both ROS and RNS inhibit Wnt signaling in cultured hearts. A and B, DKK1, β-catenin, Wnt5a and phosphorylated NFAT4 levels in cultured hearts. Experiments were repeated three times. * indicate significant difference compared with other groups.. C. Schematic of oxidative stress-mediated Wnt signaling impairment in the developing heart leading to heart defects under maternal diabetic conditions. Oxidative stress induced by maternal diabetes inhibits both the canonical and noncanonical Wnt signaling pathways through two distinct mechanisms. Maternal diabetes suppresses the canonical Wnt signaling by increasing its antagonist expression and the activity of its negative regulator whereas it inhibits the non-canonical Wnt signaling by downregulating Wnt5a.Major types of heart defects associated with gene deletion of key Wnt intermediates are indicated. p means phosphorylation.