Androgen Receptor Localization in Human Oral Mucosa: Implications for Hypospadias Surgery

BACKGROUND: Hypospadias is a congenital defect of the urethra that often requires surgical correction. Oral mucosa (OM) is commonly used as a graft material in adult and pediatric urethroplasties (revised as suggested by Reviewer #3) , but its suitability for pediatric hypospadias surgery remains uncertain. A critical concern is whether OM grafts can grow proportionally with the penis during puberty, a process driven by androgen signaling. This study investigates androgen receptor (AR) localization and responsiveness in adult human OM to provide foundational insights for its potential clinical applications in hypospadias surgery.

METHODS: Human OM samples (n=15) were collected from adult patients (aged 27-80 years) undergoing urethroplasty for hypospadias or urethral stricture disease, without hormonal or genetic profiling. AR localization was analyzed using immunofluorescence staining, while cultured human oral mucosa cells (hOMCs) were exposed to testosterone or dihydrotestosterone (DHT) to assess AR translocation. AR expression levels were quantified via RT-qPCR RESULTS: Immunofluorescence revealed predominantly cytoplasmic AR localization in human OM, with nuclear localization observed in only three samples and mixed localization in four samples. Androgen stimulation of hOMCs did not result in nuclear translocation of AR, which remained cytoplasmic. RT-qPCR demonstrated low AR expression levels in hOMCs compared to positive control.

CONCLUSION: Human OM exhibits limited androgen responsiveness, raising concerns about its ability to adapt to pubertal growth when used as a graft material in hypospadias surgery. Although current evidence on OM graft behavior during puberty is limited and biased, the relationship between androgen receptor expression and postoperative complications remains unclear. Further prospective studies are needed to assess the suitability of OM grafts and clarify the role of AR in hypospadias repair. (revised as suggested by Reviewer #3).