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Published-Ahead-of-Print May 22, 2008, DOI:10.2164/jandrol.108.004945

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Endocrine Disruptors, Genital Development and Hypospadias

Ming-Hsien Wang and Laurence S. Baskin *

* To whom correspondence should be addressed. E-mail: lbaskin{at}urology.ucsf.edu.

Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 125 live male births. Hypospadias can be defined as an anatomic defect in the formation of the urethra on the ventral aspect of the penis, an arrest in the development of the normal circumferential prepuce, and varying degrees of penile curvature. Currently, the only available treatment is surgery. If left uncorrected, especially in severe forms of hypospadias, there is risk of infertility and psychological impact such as avoidance of intimate relationships. The cause of hypospadias is largely unknown; however, current epidemiology and laboratory studies have shad new light into the etiology of hypospadias. A working hypothesis is that hypospadias is caused by a genetic susceptibility along with maternal exposure to endocrine disruptors in the first trimester of pregnancy. Specifically, some of the environmental agents are acting as antiandrogens and directly interfering with the action of testosterone. In this paper we review the normal development of the male external genitalia, the prevalence, and environmental risk factors related to hypospadias. In addition, we will discuss some of the recent laboratory findings, which contribute, to our current understanding of this disease.


Key words: antiandrogens • differentiation • external genitalia • gene expression • urogenital development






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