Endometrial Immune Cells and their Role in the Reproduction Process

Clinical tests performed in the Laboratory of Molecular Immunology of the Institute of Immunology of Vilnius University in cooperation with the Gynaecological Department of the General Surgery Center of Vilnius University Emergency Aid Hospital and Fertility Clinic, Vilnius are reviewed. Two permissions have been obtained from the Lithuanian Committee of Bioethics for carrying out the tests. The aim of the study was to determine endometrial immune cells and to evaluate their role in the reproduction process. Materials and methods. The following groups of women took part in our study: fertile women (they formed control group) (n=142), infertile women (n=121), women after miscarriage (n=35) and women with endometriosis (n=181). The following laboratory methods were used: cytological (to define the morphology of cells); flow cytometry (for detection of the phenotype of immune cells) and immunoenzyme assay – to quantify the concentration of soluble substances, such as cytokines and HLA-G molecules. Results and Conclusions. Composition of the endometrial immune cells, expression of lymphocyte and macrophage activation molecules has been changing during the menstrual cycle. In the pre-menstrual period the number of macrophages and NK cells has increased: in the stage of proliferation-7.3±2.8%; in the late stage of secretion – 13.7±3.1% and in the stage of proliferation – 18.3±5.8%, in the late stage of secretion – 51.1±9.8, respectively. The highest amount of activated macrophages expressing CD69 and CD54 surface molecules has been found in endometrium in the stage of proliferation (14.3±5.6% and 26.2±4.8%, respectively). A particular phenotype bearing CD56++ NK cells intensively expressing CD56 molecules were found in the decidual tissue. The majority of CD56++ NK cells (53.1±19.8%), on the contrary to peripheral blood cells, expressed KIR/NKAT2 molecules. It was determined that 3 day embryo released HLA-G into the growth medium. Thus, HLA-G may serve as one of the embryo implanting markers. During miscarriage in the decidual tissue, in contrary to normal pregnancy, activated and apoptosis resistant CD56++CD95-CD69+ NK cells were accumulating. Statistically significant increase of degranulated mast cells (up to 10% of all leucocytes) was found in decidual tissue in cases of undeveloped pregnancy. These cells might be assumed to be of importance in the reorganization of endometrium. Thus, we could conclude that the cellular composition of endometrium and the activity of immune cells are influenced by hormonal as well as by local immune factors. In the decidual tissue unique, belonging to a particular phenotype NK cells that regulate the invasion of trophoblast and ensure the normal course of pregnancy are accumulated. Another type of natural killers bearing cytotoxical potential participate in the pathogenesis of miscarriage