Effect of kisspeptin on mononuclear cell apoptosis, phagocytic activity of monocytes and neutrophils in pregnancy

During pregnancy, the maternal immune system undergoes a rearrangement associated with development of immune tolerance which preserves the fetus from adverse maternal immune responses and exerts their protection from pathogens. Suppression of maternal adaptive immune response is balanced by an increased influence of natural immunity, with neutrophils and monocytes being the main effector populations. Apoptosis also plays an important role during pregnancy, since activated cells may be dangerous to the developing fetus. Pregnancy hormones play a major role in this restructuring. The hypothalamic hormone kisspeptin-54 is produced by placental syncytiotrophoblast and may exert effects on pregnant women’s leukocytes, since they express a membrane kisspeptin receptor. The aim of our work was to evaluate the effect of kisspeptin-54 at the concentrations typical for physiological pregnancy on the phagocytic activity of monocytes, neutrophils, and apoptosis of peripheral blood mononuclear cells (PBMC) in women. Phagocytic activity was assessed by the degree of bioluminescence quenching of the genetically engineered luminescent E. coli K12 TG1 lux⁺ strain. Lymphocyte apoptosis was assessed in the PBMC suspension by staining with annexin-V and propidium iodide. The number of cells at the early and late stages of apoptosis in the lymphocyte gate was determined. The direction of kisspeptin-54 effects on phagocytosis depends on the cell type. This hormone inhibits phagocytosis of neutrophils. Meanwhile, their increased phagocytic potential may have fatal consequences for fetal development. Kisspeptin-54 exhibited a directly opposite effect on the phagocytosis of monocytes which are the main effectors/regulatory cells in the utero-placental compartment performing fetotrophic functions. Kisspeptin-54 increases the number of cells in the early and late stages of apoptosis. The decrease in phagocytic activity of neutrophils is associated with hormone-mediated apoptosis of neutrophils, since neutrophils are terminally differentiated cells programmed for apoptosis. Kisspeptin-54 seems to induce neutrophil apoptosis during pregnancy thus determining a decrease in their phagocytic function and preventing excessive activation that may be harmful to the mother and fetus. Thus, kisspeptin-54 regulates the functional activity of monocytes and neutrophils in different directions, ensuring a balance between protecting the maternal organism from infections and favorable development of the semi-allogeneic fetus.