期刊
TOXICOLOGY
卷 365, 期 -, 页码 25-34出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2016.07.017
关键词
Polychlorinated biphenyls; microRNA; mir-30d; Endometrial receptivity; In vitro implantation assay
资金
- National Funds for the Natural Sciences of China [81302454]
- Science and Technology Project funding in Xiamen City [3502Z20144039]
- Natural Science Foundation of Fujian Province [2016D025]
Polychlorinated biphenyls (PCBs) are ubiquitous legacy persistent pollutants and epidemiological data showed that PCB burdens were associated with failed implantation in human. However, the mechanism how PCB exposure affects the embryo implantation is not clear. Using an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial cell line lshikawa, we have shown that PCB mixture Aroclor 1254 at environmental-relevant concentrations (2.5, 12.5, and 62.5 mu M) dose-dependently impaired the endometrial receptivity by reducing the adhesion of JAR spheroid attachment and increasing the spheroid outgrowth. The receptive up-regulated micro-RNA, mir-30d was also down-regulated in endometrial cells by the exposure. Following transient transfection of mir-30d mimic, the disrupted attachment and outgrowth of JAR spheroids was partially restored in the model. By measurement of cadherin switch and vimentin expression, the PCB exposure also activated epithelial mesenchymal transition (EMT) in endometrial cells. In accordance, mir-30d mimic suppressed the EMT markers induced by PCBs. Luciferase reporter assay confirmed that the EMT regulator Snail was targeted by mir-30d, and the expression of Snail was dose-dependently up-regulated by PCB exposure. Taken together, our study revealed that PCBs may affect the receptivity of endometrial cells by impairing the interaction between receptivity-up-regulated microRNA and EMT process. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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