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Objective To identify the effect of HLA-G-containing exosomes on the secretory function of growth-promoting factors osteoglycin (OGN) and pleiotrophin (PTN) by decidual NK (dNK) cells. Methods dNK cells were co-cultured with HLA-G-containing exosomes from the villi of patients undergoing unexplained recurrent pregnancy loss (uRPL) and normal induced abortion, respectively. Sequentially, OGN and PTN of the dNK cells were determined using real time quantitative PCR and western blotting. Exosomes overexpressing HLA-G (HLA-G OE -EXO) were obtained by transfecting the villous trophoblast cell line HTR-8/Svneo with lentivirus LV-HLA-G. dNK cells were further co-cultured with HLA-G OE -EXO for detecting the expression of OGN and PTN, the culture supernatant of which was used to treat HTR-8/Svneo cells, and the proliferation of HTR-8/Svneo cells was detected by the CCK-8 assay. Results Exosomes derived from villi of patients receiving normal induced abortion significantly enhanced the expression of OGN and PTN in dNK cells compared with those from patients of the uRPL group. Besides, HLA-G OE -EXO markedly enhanced the expression of OGN and PTN in dNK cells. The culture supernatant of HLA-G OE -EXO treated dNK cells could promote the proliferation of HTR-8/Svneo cells. Conclusion Villi-derived HLA-G containing exosomes may enhance the secretion of growth-promoting factors in dNK cells.