c-Jun N-terminal kinase is upregulated in patients with hypospadias.

Objective: To investigate the expression of c-Jun N-terminal kinase (JNK) 1/2 in human hypospadiac tissue compared with that in normal penile tissue.

Materials And Methods: Penile skin tissue specimens obtained at surgery during hypospadias repair or during elective circumcision were divided into 3 groups according to the position of the urethral meatus: children with mild hypospadias (n=16), severe hypospadias (n=16), and normal controls (n=16). The expression of total and phosphorylated JNK1 and JNK2 at the messenger ribonucleic acid and protein levels were assessed using real-time quantitative polymerase chain reaction, immunochemistry, and Western blot analysis.

Results: JNK1 messenger ribonucleic acid expression and JNK1 and JNK2 phosphorylated protein levels increased significantly in subjects with mild or severe hypospadias compared with the controls (P<.05). JNK2 phosphorylated protein levels increased significantly in those with severe hypospadias compared with those with mild hypospadias (P<.05). Those with hypospadias had increased phosphorylation protein expression of JNK1/2 in the mesenchymal cell layers of the preputial subcutaneous mesenchymal cell layer.

Conclusion: Our findings suggest that JNK upregulation might contribute to the development of hypospadias and might associated with mesenchymal cell migration in the process of external male genitalia defect development.