The impact of COL1A1 and COL6A1 expressions on hypospadias and penile curvature severity

Abstract

Background: Hypospadias, the most frequent congenital male external genitalia abnormality, is usually associated with curvature of the ventral penile, i.e. chordee. Abnormality of dartos tissue has been suggested as the pathophysiology of the chordee. Collagen is one of the most abundant fibrous proteins within the extracellular matrix. In this study, we determined the expressions of collagen 1 (COL1A1) and COL6A1 in hypospadias patients and associated them with the severity of penile curvature.Methods: We involved 60 children <18 years old, consisting of 20 distal hypospadias, 20 proximal hypospadias patients, and 20 control in our institution from 2017 – 2020. The expressions of COL1A1 and COL6A1 from dartos tissue were determined by reverse-transcriptase polymerase chain reaction (qPCR). The penile curvature severity was classified as mild (<30 degree), moderate (30-60 degree), and severe (>60 degree). Results: qPCR showed that the COL1A1 and COL6A1 expressions were significantly downregulated in distal (0.88 (0.38-2.53) and 0.54 (0.16-4.35), respectively) and proximal 0.76 (0.33-2.57) and 0.57 (0.18-1.38), respectively) hypospadias groups compared to controls (1.85 (0.24-4.61) and 0.93 (0.17-4.06), respectively) with p-value of 0.024 and 0.018, respectively. Furthermore, there was a moderate correlation between COL1A1 and COL6A1 expressions (r=0.458, p<0.0001). Interestingly, the COL1A1 and COL6A1 was also significantly downregulated in the moderate and severe compared to the mild chordee groups with p-value of 0.003 and 0.037, respectively.Conclusions: Aberrant COL1A1 and COL6A1 expressions might affect the abnormality of dartos tissue and penile curvature severity in hypospadias patients.