Testosterone treatment of human foreskin in a novel transplant model

Objectives To determine whether testosterone would increase angiogenesis in human foreskin, because of the known effects of testosterone on endothelial cells and vascular endothelial growth factor expression. Surgical management of complex hypospadias in a patient who has undergone multiple procedures is technically very challenging. It is possible that therapy to increase the blood supply to this tissue could be beneficial. Methods We used a newly developed model of human skin transplantation, in which full-thickness human foreskin is transplanted subcutaneously onto the dorsum of a nude rat. At 10 days after transplantation, tissue was treated with either testosterone gel or vehicle control. After an additional 7 days, the tissue was harvested, embedded in paraffin, stained for factor VIII to assess vascularity, and examined histologically. Results The testosterone-treated tissue demonstrated increased factor VIII staining (31.14 ± 1.53 vessels per high-power field) compared with the control group (18.25 ± 2.3 vessels per high-power field; P <0.0005). Histologic analysis revealed less collagen in the testosterone-treated group compared with the control group. Conclusions Treatment of human foreskin with testosterone, in a transplant model, increased vascularity and decreased early fibrosis. Testosterone treatment may improve the surgical management of complex hypospadias repair.