Abstract
Earlier evidence suggests, that the embryo signals to the maternal immune system. Extracellular vesicles (EVs) are produced by all types of cells, and because they transport different kinds of molecules from one cell to the other, they can be considered as means of intercellular communication. The aim of this work was to test, whether the embryo is able to produce sufficient amounts of EVs to alter the function of peripheral lymphocytes. Embryo-derived EVs were identified by their Annexin V biding capacity, and sensitivity to Triton X dependent lysis, using flow cytometry. Transmission electron microscopy was used to detect EVs at the implantation site. Progesterone-induced blocking factor (PIBF) expression in embryo-derived EVs was demonstrated with immuno-electron microscopy. The % of IL-10 + murine lymphocytes was determined by flow cytometry. EVs were present in embryo culture media, but not in empty media. Mouse embryo-derived EVs adhere to the surface of both CD4+ and CD8+ murine peripheral T lymphocytes, partly, via phosphatidylserine binding. The number of IL-10+ murine peripheral CD8+ cells increases in the presence of embryo-derived EVS, and this effect is counteracted by pre-treatment of EVs with an anti-PIBF antibody, suggesting that the embryo communicates with the maternal immune system via EVs.
Highlights
Pregnancy has a profound influence on the functioning of the maternal immune system
The aim of this work was to test, whether the embryo-derived extracellular vesicles (EVs) might carry Progesterone-induced blocking factor (PIBF), and whether PIBF+ embryo-derived EVs might alter the function of peripheral lymphocytes, this way contributing to the communication between the embryo and the mother in the early stage of pregnancy
The number of Annexin V positive events was higher in embryo culture media (Fig. 1C,E in panel A), than in empty media (Fig. 1A in panel A)
Summary
Pregnancy has a profound influence on the functioning of the maternal immune system. There is evidence, that the embryo releases signals, to alter the maternal immune functions, from the earliest stages of pregnancy, the mechanism of signal transport has not been thoroughly investigated. In recent years extracellular vesicles (EVs) have received much attention. These membrane-coated structures may express phosphatidylserine (PS) in their membrane[3], which reacts with Annexin V. We showed that in vitro cultured human embryos produce detectable numbers of EVs4, it seemed plausible, that these structures might be involved in the communication between the embryo and the endometrium during implantation
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