Decidual derived exosomal miR-99a-5p targets Ppp2r5a to inhibit trophoblast invasion in response to CeO2NPs exposure

Autor: Hangtian Zhong, Yanqing Geng, Rufei Gao, Jun Chen, Zhuxiu Chen, Xinyi Mu, Yan Zhang, Xuemei Chen, Junlin He
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Particle and Fibre Toxicology, Vol 20, Iss 1, Pp 1-15 (2023)
Druh dokumentu: article
ISSN: 1743-8977
52911837
DOI: 10.1186/s12989-023-00524-y
Popis: Abstract Background The biological effects of cerium dioxide nanoparticles (CeO2NPs), a novel material in the biomedical field, have attracted widespread attention. Our previous study confirmed that exposure to CeO2NPs 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 CeO2NPs 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. Results Here, we constructed a mice primary uterine stromal cell-induced decidualization model in vitro, and detected the effect of CeO2NPs 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 CeO2NPs 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. Conclusions This study revealed the molecular mechanism by which CeO2NPs 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 CeO2NPs exposure and new ideas for studying the mechanism of damage to trophoblast cells at the decidual-foetal interface by harmful environmental or occupational factors.
Databáze: Directory of Open Access Journals
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