Hangtian Zhong, Yanqing Geng, Rufei Gao, Jun Chen, Zhuxiu Chen, Xinyi Mu, Yan Zhang, Xuemei Chen, Junlin He
{"title":"个体来源的外泌体miR-99a-5p靶向Ppp2r5a以抑制滋养细胞对CeO2NPs暴露的侵袭。","authors":"Hangtian Zhong, Yanqing Geng, Rufei Gao, Jun Chen, Zhuxiu Chen, Xinyi Mu, Yan Zhang, Xuemei Chen, Junlin He","doi":"10.1186/s12989-023-00524-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The biological effects of cerium dioxide nanoparticles (CeO<sub>2</sub>NPs), a novel material in the biomedical field, have attracted widespread attention. Our previous study confirmed that exposure to CeO<sub>2</sub>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<sub>2</sub>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.</p><p><strong>Results: </strong>Here, we constructed a mice primary uterine stromal cell-induced decidualization model in vitro, and detected the effect of CeO<sub>2</sub>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<sub>2</sub>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.</p><p><strong>Conclusions: </strong>This study revealed the molecular mechanism by which CeO<sub>2</sub>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<sub>2</sub>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.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"20 1","pages":"14"},"PeriodicalIF":7.2000,"publicationDate":"2023-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116836/pdf/","citationCount":"0","resultStr":"{\"title\":\"Decidual derived exosomal miR-99a-5p targets Ppp2r5a to inhibit trophoblast invasion in response to CeO<sub>2</sub>NPs exposure.\",\"authors\":\"Hangtian Zhong, Yanqing Geng, Rufei Gao, Jun Chen, Zhuxiu Chen, Xinyi Mu, Yan Zhang, Xuemei Chen, Junlin He\",\"doi\":\"10.1186/s12989-023-00524-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The biological effects of cerium dioxide nanoparticles (CeO<sub>2</sub>NPs), a novel material in the biomedical field, have attracted widespread attention. Our previous study confirmed that exposure to CeO<sub>2</sub>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<sub>2</sub>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.</p><p><strong>Results: </strong>Here, we constructed a mice primary uterine stromal cell-induced decidualization model in vitro, and detected the effect of CeO<sub>2</sub>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<sub>2</sub>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.</p><p><strong>Conclusions: </strong>This study revealed the molecular mechanism by which CeO<sub>2</sub>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<sub>2</sub>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.</p>\",\"PeriodicalId\":19847,\"journal\":{\"name\":\"Particle and Fibre Toxicology\",\"volume\":\"20 1\",\"pages\":\"14\"},\"PeriodicalIF\":7.2000,\"publicationDate\":\"2023-04-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116836/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Particle and Fibre Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12989-023-00524-y\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Particle and Fibre Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12989-023-00524-y","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
Decidual derived exosomal miR-99a-5p targets Ppp2r5a to inhibit trophoblast invasion in response to CeO2NPs exposure.
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.
期刊介绍：
Particle and Fibre Toxicology is an online journal that is open access and peer-reviewed. It covers a range of disciplines such as material science, biomaterials, and nanomedicine, focusing on the toxicological effects of particles and fibres. The journal serves as a platform for scientific debate and communication among toxicologists and scientists from different fields who work with particle and fibre materials. The main objective of the journal is to deepen our understanding of the physico-chemical properties of particles, their potential for human exposure, and the resulting biological effects. It also addresses regulatory issues related to particle exposure in workplaces and the general environment. Moreover, the journal recognizes that there are various situations where particles can pose a toxicological threat, such as the use of old materials in new applications or the introduction of new materials altogether. By encompassing all these disciplines, Particle and Fibre Toxicology provides a comprehensive source for research in this field.
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