Comparative Analysis of MMP-1 and α-SMA Expression in Ventral and Dorsal Dartos Tissue of Patients With Hypospadias and Chordee

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Abstract

Background Hypospadias-associated chordee is believed to result from abnormal extracellular matrix remodeling and connective tissue organization within the penile dartos fascia. However, molecular differences between ventral and dorsal dartos compartments remain poorly understood. This study aimed to compare the gene expression of matrix metalloproteinase-1 (MMP-1) and alpha-smooth muscle actin (α-SMA) between ventral and dorsal dartos tissues in patients with hypospadias and chordee. Methods A cross-sectional observational study was conducted over a 24-month period at a tertiary referral center in Indonesia. Thirty-three pediatric patients with hypospadias and chordee undergoing urethroplasty were enrolled. Ventral and dorsal dartos tissue specimens were collected intraoperatively. Relative mRNA expression of MMP-1 and α-SMA was quantified using quantitative real-time polymerase chain reaction (qRT-PCR), normalized to β-actin, and analyzed using the 2^-ΔΔCt method. Comparisons between tissue compartments were performed using appropriate statistical tests, with statistical significance defined as p < 0.05. Results Ventral dartos tissue demonstrated significantly lower MMP-1 expression than dorsal tissue (median fold change: 0.565 vs. 0.609; p = 0.035). Conversely, α-SMA expression was significantly higher in ventral tissue than in dorsal tissue (median fold change: 1.242 vs. 0.574; p < 0.001). These findings indicate distinct molecular profiles between ventral and dorsal dartos tissues in patients with hypospadias and chordee. Conclusions Significant regional differences in MMP-1 and α-SMA gene expression were identified between ventral and dorsal dartos tissues. Reduced MMP-1 expression together with increased α-SMA expression in ventral tissue suggests altered extracellular matrix remodeling and enhanced fibrotic activity that may contribute to the pathogenesis of penile curvature. These findings provide preliminary molecular evidence supporting compartment-specific biological differences within dartos tissue and warrant further investigation using protein-level analyses and functional studies.

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