Down-regulation of FGF10 in hypospadias prepuce associated with severity

Fibroblast growth factors (FGF) expressed in the genital tubercle, especially FGF8 and FGF10, may be implicated in the morphogenesis of external genitalia. We investigated the expression of FGF8 and FGF10 in hypospadias prepuce to confirm any correlation. Hypospadias was classified according to the location of the external meatus as coronal/subcoronal (mild; n=7), midshaft (moderate; n=6), or penoscrotal (severe; n=3). Prepuce tissue specimens obtained intraoperatively from hypospadias patients (H; n=16) and phimosis patients (P; n=8) between 2010 and 2016 were examined immunohistochemically by calculating the mean intensity of FGF positive cells from the papillary dermis in each of 5 randomly chosen 100μm x 100μm areas. Quantification of immunostaining was performed using ImageJ®. FGF10 was quantified by Western blotting. Median ages at surgery were 4.1 and 3.4 years for H and P, respectibely. Both FGF8 and FGF10 were expressed in the upper dermis, especially the papillary layer. FGF8 was similar; P versus mild H ( p =0.98), moderate H ( p =0.97), severe H ( p =0.77), mild H versus moderate H ( p =0.85), severe H ( p =0.91), moderate H versus severe H ( p =0.59), but FGF10 was down-regulated in H in proportion to severity (P: 13.08% versus mild H: 7.28%, moderate H: 5.01%, and severe H: 1.38%) ( p <0.05, respectively). Western blot analysis was expressed as the ratio of FGF10 protein amount per β-actin (P: 0.91 versus mild H: 0.99, moderate H: 0.65, severe H: 0.48). The down-regulation of FGF10 identified may contribute to further understanding the etiology of hypospadias and may have some possible application for treating hypospadias.