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Background  Hypospadias, the most frequent congenital male external genitalia abnormality, is usually associated with curvature of the ventral penis, i.e. chordee. Abnormality of darto tissue has been suggested as the pathophysiology of chordees. Collagen is one of the most abundant fibrous proteins within the extracellular matrix. In this study, we determined the expression of  collagen 1 (COL1A1)  and  COL6A1  in patients with hypospadias and associated them with the severity of penile curvature.    Methods  We included 60 children < 18 years old, consisting of 20 distal hypospadias, 20 proximal hypospadias patients, and 20 controls in our institution from 2017 – 2020. The expression of  COL1A1  and  COL6A1  in darto tissue was determined by reverse-transcriptase polymerase chain reaction (qPCR). The penile curvature severity was classified as mild (< 30 degrees), moderate (30–60 degrees), and severe (> 60 degrees).    Results  qPCR showed that  COL1A1  and  COL6A1  expression was significantly downregulated in the 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 -values of 0.024 and 0.018, respectively. Furthermore, there was a moderate correlation between  COL1A1  and  COL6A1  expression ( r  = 0.458,  p  < 0.0001). Interestingly,  COL1A1  and  COL6A1  were also significantly downregulated in the moderate and severe chordee groups compared to the mild chordee groups, with  p -values of 0.003 and 0.037, respectively.    Conclusions  Aberrant  COL1A1  and  COL6A1  expression might affect abnormalities in darto tissue and penile curvature severity in hypospadias patients.

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