Adverse pregnancy outcomes, including preterm birth, low birth weight, small for gestational age, intrauterine growth restriction and stillbirth,are significant determinants of infant mortality and morbidity [1, 2]. The United States has higher rates of these adverse pregnancy outcomes compared with other industrialized nations [1]. Limited studies have explored the impact of exposure to environmental pollutants on pregnancy outcomes. A recent epidemiologic study reports significant associations between exposure to trichloroethylene (TCE) and decreased birth weight [28]. TCE is a common drinking water contaminant, and is currently ranked 16th on the Superfund Priority List of Hazardous Substances [2]. The present project, which focuses on TCE impacts on the placenta and extraplacental membranes, is part of a larger transdisciplinary effort to investigate whether exposure to certain environmental contaminants, including TCE, increase a woman's risk for adverse birth outcomes. I will use in vivo and in vitro models to elucidate the mechanism of TCE-induced activation of inflammatory and oxidative stress pathways in placental cells and tissue. Because the placenta and its membranes are critical tissues for pregnancy, the present project addresses data gaps in our understanding of the mechanism by which TCE may stimulate adverse birth outcomes. My hypothesis is that exposure to trichloroethylene induces oxidative stress and inflammatory pathway activation in gestational tissues leading to adverse pregnancy outcomes. The hypothesis is based on our preliminary data that show that: 1) TCE exposure of pregnant rats significantly decreased fetal weight and induced focal areas of necrosis within the basal zone of the placenta; and 2) a principal bioactive metabolite of TCE, 1,3-dichlorovinyl cysteine (DCVC), decreased the antioxidant glutathione, increased pro-inflammatory cytokine release and increased expression of prostaglandin-endoperoxide synthase 2 (PTGS2), matrix metalloproteinases (MMPs) and redox- sensitive genes in human placental trophoblasts (HTR-8/SVneo cell line). The hypothesis will be tested by two specific aims: 1) to test the subhypothesis that exposure to TCE increases production of reactive oxygen species and activates inflammatory pathways in placental and extraplacental tissue in rat; and 2) to test the subhypothesis that DCVC is a bioactive TCE metabolite for placental toxicity. Results from this project will provide new knowledge about potential mechanisms by which environmental toxicants may contribute to adverse birth outcomes.