Is activating transcription factor 3 up-regulated in patients with hypospadias?

Abstract

Purpose: Even though hypospadias is one of the most common congenital anomalies, the cause of hypospadias is largely unknown. With regard to molecular biology and microarray technology, it appears that hypospadias is potentially related to disrupted gene expression. Genomic analysis of hypospadiac tissue indicated a potential role for activating transcription factor 3 (ATF3) in the development of this anomaly. This study prospectively examined the expression of ATF3 in tissues from 20 children with hypospadias compared with 26 normal penile skin tissue samples from elective circumcision.

Materials and methods: Prepucial tissue was obtained from children who underwent repair of hypospadias for comparison with tissue samples from children who underwent elective circumcision. Skin specimens were evaluated for the expression of ATF3 protein by immunohistochemical staining.

Results: Immunohistochemical staining for ATF3 in samples from children who underwent repair of hypospadias was significantly greater than in samples from children who underwent elective circumcision (80% vs. 11%, respectively; p<0.05).

Conclusions: Our results indicate that ATF3 is up-regulated in the penile skin tissue of boys with hypospadias, which suggests a role for this transcription factor in the development of this abnormality.

Keywords: Activating transcription factor 3; Estrogens; Genetics; Hypospadias; Urogenital abnormalities.

FIG. 1

Activating transcription factor 3 (ATF3) immunoreactivity in hypospadic and control tissues (×100). (A) There is no ATF3 immunoreactivity in circumcision control tissue. (B) ATF3 is clearly expressed in the nucleous of the cell (arrow) in the sc tissue of subcoronal hypospadic sample. (C) ATF3 protein localized in the nuclei of stromal cells (black arrow) and the vascular endothelium (white arrow) in sc tissue of mid penil hypospadic sample.