Candidate genes and their response to environmental agents in the etiology of hypospadias.

The molecular events that lead to isolated hypospadias remain largely unknown, and the etiology of this common congenital anomaly seems to be multifactorial. We have explored the response of several candidate genes to environmental agents that cause hypospadias in a mouse model. Here, we provide an overview of current findings in relation to candidate genes and their response to environmental agents, including the results of genomic analyses of both mouse and human tissues. In addition to steroid-hormone receptors, one gene of specific interest is activating transcription factor 3 (ATF3). We hypothesize a potential mechanism of action for ATF3 and other identified genes, including TGF-B.