Decidual derived exosomal miR-99a-5p targets Ppp2r5a to inhibit trophoblast invasion in response to CeO(2)NPs exposure
作者全名："Zhong, Hangtian; Geng, Yanqing; Gao, Rufei; Chen, Jun; Chen, Zhuxiu; Mu, Xinyi; Zhang, Yan; Chen, Xuemei; He, Junlin"
作者地址："[Zhong, Hangtian; Gao, Rufei; Chen, Zhuxiu; Zhang, Yan; Chen, Xuemei; He, Junlin] Chongqing Med Univ, Sch Publ Hlth, 1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China; [Zhong, Hangtian; Geng, Yanqing; Gao, Rufei; Chen, Zhuxiu; Mu, Xinyi; Zhang, Yan; Chen, Xuemei; He, Junlin] Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing, Peoples R China; [Chen, Jun] Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China"
通信作者："He, JL (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, 1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China.; He, JL (通讯作者)，Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing, Peoples R China."
来源：PARTICLE AND FIBRE TOXICOLOGY
ESI学科分类：PHARMACOLOGY & TOXICOLOGY
关键词：CeO(2)NPs; Placental development; Decidual cells; Trophoblast; Exosome-derived miRNA
摘要："BackgroundThe biological effects of cerium dioxide nanoparticles (CeO(2)NPs), a novel material in the biomedical field, have attracted widespread attention. Our previous study confirmed that exposure to CeO(2)NPs during pregnancy led to abnormal trophoblast invasion during early placental development, thereby impairing placental development. The potential mechanisms may be related to low-quality decidualization triggered by CeO(2)NPs exposure, such as an imbalance in trophoblast invasion regulators secreted by decidual cells. However, the intermediate link mediating the ""dialogue"" between decidual cells and trophoblasts during this process remains unclear. As an important connection between cells, exosomes participate in the ""dialogue"" between endometrial cells and trophoblasts. Exosomes transfer bioactive microRNA into target cells, which can target and regulate the level of mRNA in target cells.ResultsHere, we constructed a mice primary uterine stromal cell-induced decidualization model in vitro, and detected the effect of CeO(2)NPs exposure on the expression of decidual-derived exosomal miRNAs by high-throughput sequencing. Bioinformatics analysis and dual-luciferase reporter assays were performed to identify target genes of the screened key miRNAs in regulating trophoblast invasion. Finally, the role of the screened miRNAs and their target genes in regulating trophoblast (HTR-8/SVneo cells) invasion was confirmed. The results showed that CeO(2)NPs exposure inhibited trophoblast invasion by promoting miR-99a-5p expression in decidual-derived exosomes, and Ppp2r5a is a potential target gene for miR-99a-5p to inhibit trophoblast invasion.ConclusionsThis study revealed the molecular mechanism by which CeO(2)NPs exposure inhibits trophoblast invasion from the perspective of decidual derived exosomal miRNAs. These results will provide an experimental basis for screening potential therapeutic targets for the negative biological effects of CeO(2)NPs exposure and new ideas for studying the mechanism of damage to trophoblast cells at the decidual-foetal interface by harmful environmental or occupational factors."