BACKGROUND Systemic inflammation caused by dysfunctional macrophages is a crucial pathogenetic event in preeclampsia PETrophoblast-derived extracellular vesicles T-EVs are potent immune cell signaling

In this study, the researchers aimed to investigate the effect and mechanism of trophoblast-derived extracellular vesicles (T-EVs) on macrophage polarization and its role in the development of preeclampsia (PE). Preeclampsia is a condition characterized by systemic inflammation caused by dysfunctional macrophages.

The researchers first determined the phenotypes of placental macrophages using flow cytometry and immunochemistry. They found that in the preeclamptic placenta, macrophages shifted from the M2 phenotype (associated with anti-inflammatory responses) to the M1 phenotype (associated with pro-inflammatory responses).

Next, T-EVs were isolated using placental alkaline phosphatase antibody and characterized using transmission electron microscopy and nanoparticle tracking analysis. The researchers found that T-EVs from women with PE (PE-EVs) significantly upregulated gene markers associated with the M1 phenotype and downregulated CD163 expression (a marker of M2 phenotype) in macrophages compared to T-EVs from women with normal pregnancies (NP-EVs).

To explore the mechanism by which T-EVs modulate macrophages, the researchers performed correlation analysis between the lipidomics of T-EVs and the transcriptome of macrophages treated with PE-EVs or NP-EVs. They found that 37 lipids altered in PE-EVs significantly affected classical inflammatory biological pathways in macrophages.

Finally, animal experiments were conducted to investigate the relationship among PE, T-EVs, and macrophages. The researchers found that PE-EVs triggered PE-like symptoms in pregnant mice, which were alleviated after macrophage depletion.

In conclusion, this study suggests that T-EVs from women with PE can induce macrophage imbalance polarization, leading to the development of preeclampsia. This finding highlights T-EVs as a potential target for intervention in the prevention and management of PE