Hypospadias is a birth defect that affects about 1 in every 125 males born (Paulozzi et al., 1997; CDC 2004). Because the urethral tube does not close properly, an opening forms on the ventral side of the penis and, in some cases, in the perineum. Maternal exposure to Endocrine Disrupting Chemicals (EDCs) is correlated with the frequency of hypospadias in males (Fernandez et al., 2007). Initial findings in the Cohn lab show that vitamin E reduces the severity of hypospadias in mice that have been treated with the EDC, vinclozolin, during embryonic development. Vinclozolin acts as an antagonist to androgen receptors (ARs), meaning that the hormones that masculinize the genital tubercle are inhibited. It’s known that ARs are required for cell proliferation to occur properly in the urethral epithelium (Petiot et al, 2005). Also, it has recently been found that the disruption of ARs can negatively affect apoptosis leading to hypospadias (Baskin et al., 2001b). I will test the hypothesis that Vitamin E reduces hypospadias by altering apoptosis and cell proliferation occurring in the tubercle. Pregnant female mice will be gavaged with Corn Oil (vehicle control), Vinclozolin, or Vinclozolin and Vitamin E, and pups will be taken at embryonic stages E15.5 and E17.5, so I can characterize how cell proliferation and apoptosis differ prior to and during sexual differentiation. Immunohistochemistry will be performed using an antibody against phospho-histone H3 (PHH3) to label proliferating cells in the late G2/M phase of the cell cycle and using caspace3 which labels cells undergoing apoptosis. The purpose of this research is to determine the developmental processes through which vitamin E reduces the severity of hypospadias. Because pregnant women are often exposed to EDCs, this research could be the first step in the development of a prenatal supplement to prevent hypospadias.