RE08 : p, p-DDT induce apoptosis in human endometrial stromal cells through oxidative stress

Objective: Organochlorines, such as dichlorodiphenyltrichloroethane (DDT), can cause a various effects on the cells by triggering estrogen receptor. Because of their long half-lives, DDT and its metabolites are still found throughout the world. DDT is associated with reduced mean luteal-phase length, spontaneous abortion, early age at menopause, and reduced duration of lactation. However, their effect on endometrium is not clearly revealed. Here we studied whether DDT causes oxidative stress and apoptosis in human endometrial cells. Methods: Human endometrial stromal cells were obtained from reproductive aged women with normal menstrual cycle. Our study was design to find out whether DDT causes oxidative stress and apoptosis and to investigate its effects on modulators of antioxidative enzymes and caspase pathway in human endometrial cell. Also we have studied association between DDT and estrogen receptors (ER) and NF-B pathways in human endometrium. Results: From flow cytometric analysis, we found that DDT contributed to apoptosis. Fluorescence microscopy showed that DDT induced formation of apoptotic bodies and DNA fragmentation. After exposure to DDT, Bcl-2 with anti-apoptotic potential decreased and BAX, an apoptotic regulator, showed a dose-dependent increase. The expression of caspase-3, 6, 8, and 10 were also significantly increased. Treatment of endometrial cells with DDT resulted in a significant increase in DCF fluorescence and showed significant decrease in GPX and SOD expression. Regarding ER, DDT down-regulated the expression of ER- and reversed by antagonist treatment. Conclusion: Our study showed that when DDT is exposed to human endometrial cells, apoptosis can occur by producing oxidative enzyme and modulating estrogen receptors. Changes in mediators of antioxidative enzymes and caspase pathway also lead to apoptosis. These reactions will have significant effects on human endometrial environment which can determine the pathogenesis of diseases involving endometrium.