Hypospadias and urethral development

Purpose: Hypospadias is a common congenital anomaly that may be treated wit h surgical reconstruction. In the majority of cases the etiology remains el usive. Although androgens are clearly critical for penile development, defe cts in androgen metabolism and/or the androgen receptor explain only a smal l subset of cases of hypospadias. Strategies are presented for understandin g the etiology of hypospadias. Materials and Methods: Current scientific reports on the etiology of hyposp adias were reviewed, and the embryology and possible mechanisms of urethral and penile formation are presented. Results: A new theory of glandular human urethral development via endoderma l cellular differentiation is proposed to replace the classic explanation o f ectodermal intrusion. Conclusions: Careful studies of penile and urethral development have led to a better understanding of genital embryology. Future areas of study, such as endocrine disrupters, mesenchymal-epithelial interactions and mechanisms of penile growth, are proposed to explain the etiology of hypospadias.