Embryoconditioned media alter the effector functions of natural killers in vitro

NK cells represent the predominant endometrial lymphocyte subpopulation. During implantation phase, NK cells participate in communications with embryo, thus influencing successful implantation. However, there is currently a lack of literature data regarding potential influence of pre-implantation embryos on functional activity of NK cells. The role of NK cells in the utero-placental contact zone is to control trophoblast invasion, stimulate or limit it. Cytokines secreted by both embryo and NK cells, e.g., IL-1b, IL-6, IL-8, GM-CSF, and IP-10, have been shown to stimulate migration and invasion of trophoblast cells Therefore, the purpose of this study was to develop a cellular diagnostic technology for predicting reproductive failure by investigating the effect of the spent, embryo-conditioned culture media (ECM) on the cytotoxic activity of NK cells towards trophoblast JEG-3 cells using an in vitro cytotoxicity model. We have found that the death rate of Jeg-3 cells after co-culture with NK-92 cells was higher than the rates of spontaneous Jeg-3 cell death. In general, the series of spent ECM, which were not divided into groups by quality of the cultured embryos, have reduced the death of Jeg-3 cells when co-cultured with NK-92 cells. We have revealed that ECM from grade A (excellent-quality) embryos reduce the effector functions of natural killer cells against JEG-3 trophoblast cells. Hence, we suggest that the embryos with highest implantation potential (grade A) secrete factors that suppress NK cell cytotoxicity toward trophoblast cells, thereby promoting embryonic survival and its successful implantation. Previously, we have detected cytokines affecting NK cell functions IL-6, IL-8, IL-1b, IL-10, IP-10 and GM-CSF secreted by excellent quality embryos into a spent culture medium. Thus, excellent-quality embryos with the greatest implantation potential secrete factors that modulate NK cell effector functions at the maternal-fetal interface. The method of assessing the embryo quality by means of functional model is, generally, consistent with morphological approach to the quality assessment of embryos and may be recommended for usage in clinical practice.

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