title: Polychlorinated biphenyls impair endometrial receptivity in vitro via regulating mir-30d expression and epithelial mesenchymal transition.
abstract: 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 Ishikawa, we have shown that PCB mixture Aroclor 1254 at environmental-relevant concentrations (2.5, 12.5, and 62.5μM) 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 Snai1 was targeted by mir-30d, and the expression of Snai1 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.
authors.affiliation: Reproductive Medicine Center, The Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian, 361002, China.
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Cai
authors.affiliation: Reproductive Medicine Center, The Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian, 361002, China.
authors.forename: Lan-Lan
authors.initials: LL
authors.lastname: Liu
authors.affiliation: Reproductive Medicine Center, The Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian, 361002, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Reproductive Medicine Center, The Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian, 361002, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Jiang
authors.affiliation: Reproductive Medicine Center, The Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian, 361002, China.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Qiu
authors.affiliation: Reproductive Medicine Center, The Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian, 361002, China.
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Sha
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors.forename: Chong-Gang
authors.initials: CG
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors.forename: Zheng-Hong
authors.initials: ZH
authors.lastname: Zuo
authors.affiliation: Reproductive Medicine Center, The Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian, 361002, China. Electronic address: rjz174@126.com.
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Ren
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D010064:Embryo Implantation / Q000187:drug effects; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014746:Vimentin; D020111:Chlorodiphenyl (54% Chlorine); D011078:Polychlorinated Biphenyls
keywords: Endometrial receptivity; In vitro implantation assay; Polychlorinated biphenyls; microRNA; mir-30d