ABSTRACT
INTRODUCTION: Hypospadias is a common malformation of the genitourinary system and is thought with a complex interplay between genetics and environmental factors likely contributing to its pathogenesis. This study aimed to investigate the receptor gene expressions of sex hormones, FGFR2, FGF8 and BMP7 and DNA methylations in these genes as an epigenetic mark, which may play a role in the etiology of hypospadias. MATERIAL AND METHODS: The samples from the foreskin of 20 patients with hypospadias and 20 healthy children who underwent circumcision operations were collected. AR, ESR1, FGF8, FGFR2 and BMP7 gene expressions and DNA methylation rates of these genes were investigated in tissues. RESULTS: While ESR1, FGFR2 and BMP7 gene expressions were found to be significantly higher in the hypospadias group, AR gene expression was found to be lower. In the hypospadias group, DNA methylation rates were found to be significantly higher in the ESR1, FGF8 and FGFR2 genes, but lower in the AR gene (Table). DISCUSSION: Recent clinical studies suggest that epigenetic modifications may play a significant role in genital development, potentially contributing to the etiology of hypospadias. Our recent study demonstrated significant differences in foreskin AR, ESR1, and FGFR2 gene expression between patients with hypospadias and controls. To address this, the present study investigated DNA methylation levels of these same genes in hypospadias patients, hypothesizing that epigenetic modifications might be responsible for the observed gene expression changes. We again observed abnormalities in AR, ESR1, and FGFR2 gene expression in hypospadias patients. Furthermore, we found that DNA methylation patterns associated with these genes differed significantly between hypospadias and control groups. CONCLUSIONS: Our study demonstrates significant alterations in DNA methylation of sex hormone receptor genes (ESR1 and AR), FGFR2, and FGF8, which correlate with abnormal expression of these genes in hypospadias cases. These findings suggest a potential role for epigenetic modifications in hypospadias etiology.
