is an environmental contaminant that has been shown to have antiandrogenic properties in vivo. Interestingly, DBP does not bind the androgen receptor in vitro so its mechanism of action, which is currently unknown, is likely mediated via a pathway different from that of other classic antiandrogens such as flutamide. The developing male fetus is very sensitive to alterations in androgen levels and even a slight perturbation by an antiandrogen may have profound long-lasting effects. When exposed to DBP during a late gestational window, the period of male reproductive tract development, males exhibit an altered reproductive tract phenotype when examined at postnatal day 100. These malformations include partially to completely absent epididymides, absent vasa deferentia and hypospadias. In addition, males exposed on GD 12 - 21 have decreased anogenital distances and increased incidence of thoracic nipple retention. To better understand the time course of development of DBP-induced lesions and the molecular alterations that precede these change, studies will be undertaken in the rat using an in utero exposure model. The proposed studies will test the hypothesis that there is altered gene expression of the fetal testicular steroidogenic enzymes and that it is alterations in these enzymes that lead to altered hormone levels and subsequent development of male reproductive tract lesions. A time course study will also be undertaken to better understand lesion development in DBP-exposed males. It is hoped that the data gained through these studies will help broaden our understanding of phthalate-induced reproductive lesions in the male rat and help determine the risk to humans.
