Macrophage-derived exosomes promote proliferation, migration, and invasion of endometrial stromal cells in endometriosis and are associated with exosomal lncRNA ZFAS1: A pilot translational study

Endometriosis (EMs) is a prevalent gynecological disorder affecting reproductive-age women. Exosomes secreted by peripheral blood macrophages may participate in EMs progression. In this pilot translational study, exosomes from peripheral blood macrophages obtained from patients with EMs (n = 3) and control patients (n = 3) were isolated by ultracentrifugation, identified by transmission electron microscopy and exosomal markers, and cocultured with endometrial stromal cells. Quantitative reverse transcription polymerase chain reaction was used to detect long noncoding RNA zinc finger antisense 1 (ZFAS1) expression in macrophage-derived exosomes. Cell proliferation, migration, invasion, and apoptosis were evaluated using Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, wound healing, transwell, and flow cytometry assays. Gain- and loss-of-function experiments were performed in stromal cells to examine the biological role of ZFAS1. EMs-derived macrophage exosomes promoted endometrial stromal-cell proliferation, migration, and invasion and inhibited apoptosis compared with the blank and control-exosome groups. long noncoding RNA ZFAS1 expression was higher in EMs-derived exosomes than in control exosomes. In stromal cells, ZFAS1 overexpression enhanced proliferation, migration, and invasion and reduced apoptosis, whereas ZFAS1 knockdown produced the opposite effects. Macrophage-derived exosomes were associated with an aggressive stromal-cell phenotype, and exosomal ZFAS1 may contribute to this process. Because of the very small patient sample size and limited exosome characterization, these findings should be considered preliminary and hypothesis-generating.