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Published on: August 4, 2021
miR-196a-5p-Rich Extracellular Vesicles from Trophoblasts Induce M1 Polarization of Macrophages in Recurrent
Jing Zhang1, Yu Tao1, Renfei Cai1
1Department of Assisted Reproduction, The Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Purpose:
Numerous studies have described the presence of crosstalk between trophoblasts and macrophages and the critical role it plays in recurrent miscarriage (RM). However, the mechanism of trophoblast-derived extracellular vesicle (EV) miRNAs and their interactions with decidual macrophages in the pathogenesis of RM remains unclear.
Materials And Methods:
miRNA-seq was used to identify the differentially expressed miRNAs between RM patients and healthy controls. qPCR and in situ hybridization assays were performed to analyze the expression levels of miR-196a-5p in RM. THP-1 cells were treated with EVs, and qPCR and flow cytometry were performed to explore the polarization of macrophages. To explore the crosstalk between trophoblasts and macrophages, a coculture model and a series of cell function assays were performed.
Results:
We first demonstrated that miR-196a-5p expression was higher in the cytotrophoblasts of villous tissues and plasma EVs from RM patients. miR-196a-5p derived from trophoblasts could be transferred into macrophages via EVs to induce M1 polarization via IκBα-mediated NF-κB pathway. Moreover, we found that M1 macrophages induced by EV miR-196a-5p derived from trophoblasts conversely regulated the proliferation, migration, and apoptosis of trophoblasts via TNF-α.
Conclusions:
This study indicated that trophoblast-derived EV miR-196a-5p was positively associated with RM and functioned by regulating the crosstalk between trophoblasts and macrophages. These findings may attribute to identify a novel biomarker specific for RM.
Insights
Trophoblast extracellular vesicle miR-196a-5p promotes M1 macrophage polarization, contributing to recurrent miscarriage (RM) by altering trophoblast function. This highlights a novel biomarker for RM diagnosis.
Area of Science:
- Reproductive immunology
- Molecular biology
- Cellular communication
Background:
- Recurrent miscarriage (RM) involves complex interactions between trophoblasts and macrophages.
- The precise mechanisms of extracellular vesicle (EV)-mediated miRNA transfer and their impact on decidual macrophages in RM pathogenesis are not fully understood.
Purpose of the Study:
- To elucidate the role of trophoblast-derived EV miRNAs in the interaction with decidual macrophages during recurrent miscarriage.
- To investigate the specific function of miR-196a-5p in the pathogenesis of RM.
Main Methods:
- Differential miRNA expression profiling (miRNA-seq) in RM patients and controls.
- Quantitative PCR (qPCR) and in situ hybridization for miR-196a-5p analysis.
- Macrophage polarization studies using THP-1 cells treated with EVs and coculture models.
Main Results:
- Elevated miR-196a-5p levels were observed in trophoblasts and plasma EVs of RM patients.
- Trophoblast-derived EVs transferred miR-196a-5p to macrophages, inducing M1 polarization via the IκBα-mediated NF-κB pathway.
- M1 macrophages, activated by EV miR-196a-5p, negatively impacted trophoblast proliferation, migration, and apoptosis through TNF-α signaling.
Conclusions:
- Trophoblast-derived EV miR-196a-5p is associated with RM and mediates crosstalk with macrophages.
- This pathway highlights a novel mechanism in RM pathogenesis.
- miR-196a-5p presents potential as a specific biomarker for recurrent miscarriage.
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