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

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

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

Part Fibre Toxicol. 2023 Apr 20;20(1):14. doi: 10.1186/s12989-023-00524-y.

Authors

Hangtian Zhong^#^{1

2}, Yanqing Geng^#², Rufei Gao^{1

2}, Jun Chen³, Zhuxiu Chen^{1

2}, Xinyi Mu², Yan Zhang^{1

2}, Xuemei Chen^{1

2}, Junlin He^{4

5}

Affiliations

¹ School of Public Health, Chongqing Medical University, No.1, Yi Xue Yuan Road, Yuzhong District, Chongqing, 400016, China.
² Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China.
³ College of Pharmacy, Chongqing Medical University, Chongqing, China.
⁴ School of Public Health, Chongqing Medical University, No.1, Yi Xue Yuan Road, Yuzhong District, Chongqing, 400016, China. hejunlin@cqmu.edu.cn.
⁵ Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China. hejunlin@cqmu.edu.cn.

^# Contributed equally.

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.

Keywords: CeO2NPs; Decidual cells; Exosome-derived miRNA; Placental development; Trophoblast.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Movement
Cell Proliferation
Female
Mice
MicroRNAs* / genetics
MicroRNAs* / metabolism
Placenta / metabolism
Pregnancy
Trophoblasts* / metabolism

Substances

MicroRNAs