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

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.