The Effect of Trichloroethylene on Adverse Birth Outcomes.

Effect of trichloroethylene on the placenta;Public Health;Health Sciences;Toxicology

Hassan, ImanMeeker, John D. ;

University of Michigan

关键词: Effect of trichloroethylene on the placenta;    Public Health;    Health Sciences;    Toxicology;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/113631/ihass_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Trichloroethylene (TCE) is a chlorinated solvent and a widespread environmental pollutant implicated in adverse reproductive outcomes in humans. TCE toxicity primarily occurs through its biotransformation to toxic metabolites, including S-(1,2-dichlorovinyl)-L-cysteine (DCVC), which induce oxidative stress and inflammation in the liver and kidney. This thesis used both in vivo and in vitro approaches to test the hypothesis that TCE induces oxidative stress-mediated inflammation in gestational tissues, which contributes to adverse pregnancy outcomes.To investigate TCE-induced oxidative stress and inflammation in gestational tissues, pregnant Wistar rats were exposed daily to 480 mg/kg of TCE from gestational day 6 – 16. Placenta, maternal serum, and amniotic fluid were collected prior to onset of parturition. Exposure to TCE significantly decreased average fetal weights, increased placental 8-hydroxyguanosine, a biomarker of oxidative DNA damage, and increased placental global 5-hydroxymethylcytosine, a marker of DNA methylation changes. A significant increase in interleukin (IL)-6 levels in maternal serum was observed, and immunohistochemistry analysis showed presence of neutrophils in the decidua. These results suggest that TCE exposure in vivo induces systemic inflammation and oxidative stress in the placenta, which can lead to adverse pregnancy outcome. Moreover, DCVC, the bioactive metabolite of TCE, was detected in the amniotic fluid by HPLC/MS/MS, suggesting that the placenta may be capable of metabolizing TCE to DCVC. The effect of DCVC on proinflammatory cytokine release and stimulation of reactive oxygen species (ROS) was tested in human placental cells (HTR-8/SVneo). Results show a direct stimulatory effect of DCVC on release of IL-6. DCVC induced mitochondrial dysfunction and stimulated ROS. DCVC-induced IL-6 release was inhibited by the antioxidants (±)α-tocopherol and deferoxamine, implicating the involvement of ROS in stimulation of IL-6 release.In conclusion, results from the present study show that exposure to TCE stimulates oxidative stress and inflammation in gestational tissues and cells. Because oxidative stress and inflammation have been associated with adverse birth outcomes, these data provide support for a plausible biological explanation for TCE exposure associations with poor pregnancy outcomes. As such, this thesis provides new knowledge about the potential mechanisms by which TCE and other environmental contaminants may contribute to adverse pregnancy outcomes.