Citation

Trichloroethylene (TCE) is a common environmental pollutant associated with adverse reproductive outcomes in humans. TCE intoxication is primarily through its biotransformation to bioactive metabolites, including S-(1, 2-dichlorovinyl)-L-cysteine (DCVC). TCE induces oxidative stress and inflammation in the liver and kidney. Although the placenta is capable of xenobiotic metabolism, and oxidative stress and inflammation in placenta have been associated with adverse pregnancy outcomes, TCE toxicity in the placenta remains poorly understood. We determined the effects of DCVC using the human extravillous trophoblast cell line HTR-8/SVneo. Exposure to 10 and 20 M DCVC for 10 h increased reactive oxygen species (ROS) as measured by carboxydichlorofluorescein fluorescence. Moreover, 10 and 20 M DCVC increased mRNA expression and release of IL-6 after 24-h exposure, and these responses were inhibited by the cysteine conjugate beta-lyase (-lyase) inhibitor aminooxyacetic acid and by treatments with antioxidants (-tocopherol and deferoxamine), suggesting that DCVC-stimulated IL-6 release in HTR-8/SVneo cells is dependent on -lyase metabolic activation and increased generation of ROS. The HTR-8/SVneo cells exhibited decreased mitochondrial membrane potential at 5, 10, and 20 M DCVC at 5, 10, and 24 h, showing that DCVC induces mitochondrial dysfunction in HTR-8/Svneo cells. The present study demonstrates that DCVC stimulated ROS generation in the human placental cell line HTR-8/SVneo and provides new evidence of mechanistic linkage between DCVC-stimulated ROS and increase in the proinflammatory cytokine IL-6. Because abnormal activation of cytokines can disrupt trophoblast functions necessary for placental development and successful pregnancy, follow up investigations relating these findings to physiologic outcomes are warranted.