Evaluation of sex hormone receptors in the prepuce and tunica dartos according to the morphological features of the glans and meatus in children with Hypospadias

Hypospadias is an anatomical anomaly of the ventral surface of the penis. Although many environmental and genetic factors are thought to cause hypospadias, there is no study that fully explains its exact pathogenesis. Our study was conducted prospectively at the Department of Pediatric Surgery, Faculty of Medicine, Manisa Celal Bayar University, using tissues obtained from prepubertal hypospadias cases operated between 2022–2024 and from prepubertal cases who underwent routine circumcision. During the operation, samples were taken from the inner prepuce (IP) and outer prepuce (DP), ventral dartos (VD) and dorsal dartos (DD), urethral epithelium (UE), and the Firlit collar (FY), and these samples were histopathologically evaluated in terms of androgen receptors (AR) and estrogen receptors (ER). Immunohistochemical staining for AR and ER was performed on the tissue samples taken during the operation from all patients. Control group samples were obtained from the circumcised cases. Receptor levels in all tissues were semi-quantitatively evaluated using the modified quick score (mQuickscore). In our study, AR and ER levels in the prepuce were found to be lower in proximal hypospadias compared to distal hypospadias. In distal hypospadias, they were also found to be lower than in the control group. When AR/ER levels between VD and DD were compared in each hypospadias case, levels in VD were found to be significantly lower. In addition, when prepuce and dartos tissues were compared in the MIP variant, where the prepuce is intact, and in the control group, receptor levels in the MIP group were found to be lower than in the control group. In the group with a V-shaped defective prepuce without hypospadias and the control group, receptor levels in the prepuce and dartos tissues were found to be similar. As a result, in our study, although similar AR levels to the control group were expected in the MIP variant due to the intact prepuce, on the contrary, AR and ER expression levels gave results similar to hypospadias. In V-shape prepuce cases without hypospadias, although receptor levels were expected to resemble hypospadias, findings similar to the normal circumcision group were obtained. It was found that in the etiology of hypospadias, hormonal receptor levels vary not only according to the location of the meatus but also according to the related tissues. These results support that hypospadias is a complex developmental disorder that affects not only the local area but also all penile tissues.