Open AccessMesenchymal stem cells‐derived exosomes improve pregnancy outcome through inducing maternal tolerance to the allogeneic fetus in abortion‐prone mating mouse
Author(s) -
Xiang YanJie,
Hou YanYan,
Yan HongLi,
Liu Hui,
Ge YanXin,
Chen Na,
Xiang JianFeng,
Hao CuiFang
Publication year - 2020
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1002/kjm2.12178
Subject(s) - medicine , mesenchymal stem cell , andrology , microvesicles , pregnancy , fetus , tumor necrosis factor alpha , abortion , immunology , endocrinology , pathology , biology , microrna , genetics , gene , biochemistry
Recurrent pregnancy loss (RPL) is three or more times of consecutive spontaneous loss of pregnancy. The underlying cause is complicated and the etiology of over 50% of RPL patients is unclear. In the present study, bone marrow mesenchymal stem cells were isolated from CBA/J female mice and exosomes were isolated from cell culture medium by ultracentrifugation. CBA/J female mice were paired with male DBA/2 to generate abortion prone mouse model, and CBA/J females paired with male BALB/c mice were used as control. Exosomes were injected through uterine horns into pregnant CBA/J mice on day 4.5 of gestation in abortion‐prone matting. On day 13.5 of pregnancy, abortion rates were calculated and the level of transforming growth factor‐β (TGF‐β), interleukin 10 (IL‐10), interferon g (IFN‐γ), and tumor necrosis factor a (TNF‐α) in CD4+ T cells and macrophages in deciduas were evaluated by flow cytometry. Exosomes injection improved the pregnancy outcomes in abortion prone mice. The IL‐4 and IL‐10 levels on CD4+ T cells were upregulated in the maternal–fetal interface; meanwhile, the TNF‐α and IFN‐γ levels on CD4+ T cells were reduced. The IL‐10 level was increased and IL‐12 was reduced on the monocytes that separated from deciduas. miR‐101 level was increased in the CD4+ T cells in the deciduas. In conclusion, the treatment of ESCs‐derived exosomes modulates T cells' function and macrophages activities in the maternal–fetal interface that resulted in a decreased embryo resorption rate, and provides a therapeutic potential to treat RPL.