Investigation of genes responsible for isolated hypospadias etiology and epigenetic modifications

Hipospadias is a congenital anomaly which the urethral opening is not properly positioned at the tip of the penis. It is the second most common congenital disorder in boys after cryptorchidism, and the most common malformation of the penis. It is considered a complex disease due to the involvement of both genetic and environmental factors. In order to investigate the etiology of hypospadias, gene expression and DNA methylation of AR, ESR-1, FGFR-2, FGF-8, and BMP-7 were investigated in the prepuce tissue of 20 hypospadias and 21 circumcision patients who underwent surgery at the Trakya University Pediatric Surgery Clinic. In the hypospadias group, AR 1 gene expression and DNA methylation were significantly decreased. ESR-1 gene expression and DNA methylation were significantly increased in hypospadias patients. FGFR-2 gene expression and DNA methylation were significantly increased in hypospadias patients. BMP-7 gene expression was significantly increased in hypospadias patients, but no significant difference was found in DNA methylation. FGF-8 gene expression showed no significant difference, but DNA methylation was significantly decreased in hypospadias patients. The results of our study suggest that epigenetic modifications caused by environmental exposures may lead to the development of isolated hypospadias by regulating gene expression. Further studies in larger populations will help to understand the etiology of hypospadias, develop treatment options beyond surgical repair, and perhaps even prevent the development of hypospadias.