The impact of COL1A1 and COL6A1 expression 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 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.

Expression of mRNA vascular endothelial growth factor in hypospadias patients

“…Several studies have proved inelastic dartos tissue in hypospadias. The abnormal findings were found in smooth muscle fiber [ 20 ], collagen I and VI [ 4 ], total collagen, elastin, and reticulin [ 6 ]. Even though dartos tissue has abnormal development of some ECM structure, this study found that dartos tissue has well vascularization.…”

“…There are contrasting studies of histopathological aspects of connective tissue in patients with hypospadias. The dartos fascia of hypospadias had abnormal tissue that gave it the thick and inelastic character [ 4 , 5 ]. Inelastic dartos fascia tissue in patients diagnosed with hypospadias is a pathological tissue [ 4 , 6 , 7 ].…”

“…The dartos fascia of hypospadias had abnormal tissue that gave it the thick and inelastic character [ 4 , 5 ]. Inelastic dartos fascia tissue in patients diagnosed with hypospadias is a pathological tissue [ 4 , 6 , 7 ].…”

The effectiveness of penile curvature treatment by cavernous body rotation and plication of the tunica albuginea

“…There are four main mechanisms of congenital curvatures development: cutaneous or subcutaneous chord, the disproportion of the corpus cavernosum, or congenitally short urethra [ 2 ]. The congenital type is genetic; aberrant expression of COL1A1 and COL6A1 affects tunica dartos abnormalities and the severity of curvature [ 4 ].…”

“…Based on severity the curvature can be insignificant (less than 20 degrees), mild (20–30 degrees), moderate (30–60 degrees), and severe (more than 60 degrees) [ 4 , 5 ].…”