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Problem: Granulysin (GNLY) is a cytotoxic molecule mostly present in decidual natural killer (NK) cells. Blighted ovum (BO) and missed abortion (MA) represent the early pathological pregnancies with hindered development of the embryoblast or a dead embryo. We investigated the GNLY-mediated apoptotic mechanism potentially responsible for delayed termination of pregnancy., Method of Study: We performed immunohistological and immunofluorescence labeling of decidual tissues (GNLY, Apaf-1, NF-κB). NKG2A expression was analyzed by flow cytometry and GNLY mRNA by RT-qPCR., Results: The GNLY labeling intensity (H score) was lower in the nuclei of trophoblast cells in BO and MA. GNLY gene levels were inversely detected in BO and MA. A decreased decidual NK cell percentage was found in MA. NK cells from pathological pregnancies expressed lower NKG2A levels. The highest frequency of Apaf-1 was found in trophoblast cells of MA. NF-kB was highly expressed in decidual cells of BO., Conclusion: The reduced activation of GNLY-mediated killing might be implicated in the slower rejection of trophoblast cells in BO and MA. A decreased authentic decidual NK cell number could be responsible for low cytotoxicity against trophoblast cells in MA. In BO, trophoblast cells have a higher survival potential due to increased NF-kB expression., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/aim: Recurrent or habitual missed abortions (RMA) are defined as three or more consecutive abortions. In the first trimester of pregnancy habitual missed abortions occur in about 1% of population. The aim of this immunohistochemical study of decidua in RMA of unknown etiology was to identify subpopulations of decidual lymphocytes in recurrent miscarriages and compare the distribution of immunocompetent cells in artificial abortions and RMA. Methods. The study included 30 women with at least 2 consecutive miscarriages in the first trimester of pregnancy. Curettements of the third missed abortion were immunohistochemically analyzed. The control group consisted of 20 women without loaded reproductive anamnesis, with the abortion for social reasons. Criteria for exclusion from the study were diagnosed uterine anomalies, positive screening for thrombophilia and women who suffered from diabetes mellitus and disorders in the function of the thyroid gland. Immunophenotyping was performed by immuno-alkaline phosphatase (APAAP) using monoclonal antibodies: CD 30, CD 45 RO, CD 56 and CD 57, CD 68., Methods: The number of missed abortions (1,223) was on the average 9.7% of all deliveriies during the test period. Among them RMA were registered in 52 (4.2%) patients and in 30 (57%) the exact etiology of abortions was not determined. RMA was most common in the 25-34 years of age group. The largest number of RMA showed the ultrasound characteristics of missed abortion in 60% of cases and was in nulliparous patients (76.7%). The number of NK CD56 positive cells did not differ significantly between the types of abortion. In the decidual tissue, a number of NK CD57 positive cells was significantly higher in missed abortions compared to artificial interruptions (p < 0.01). In artificial termination of pregnancy there was an absolute predominance of CD45RO lymphocyte subpopulations, whereas in the RMA group there was slightly greater predominance of CD30 positive cells. The completed analysis showed a significantly higher number of CD68 positive macrophages in a decidual tissue of RMA pregnancy (p < 0.01)., Results: The number and phenotypic structure of NK cells are significantly different in normal pregnancy decidua and in RMA. The NK cell dominance is present in the RMA group, in favor of CD56+ and CD 57 of subpopulations with increased CD30 of T lymphocyte subpopulations. Macrophages are more numerous in the decidua of pregnancies ended in abortion, so the cause to RMA of unknown etiology in a number of cases could be disregulation of immunocompetent cells.

Problem: Increased peripheral blood natural killer (NK) cells are associated to immune-mediated abortion, but their diagnostic value when measured at the time of miscarriage is unknown., Method of Study: In women with therapeutic (A = 79) or elective (C = 34) pregnancy termination, the NK-cell percentage was measured before and 5 days after curettage. Additionally, immune-mediated lesions (scored 0-3) and CD56(+) and CD16(+) decidual NKs (scored 1-3) were detected on the abortion material., Results: Aborters differed from controls in histological scores (P = 0.000) and in NK percentage (>12%) only in the measurement 5 days after the operation (P = 0.038). In comparison to histological lesions, NK measurement was found to have sensitivity 70%, specificity 73.68%, positive prognostic value 89.39% and negative prognostic value 43.75%., Conclusion: An Increased NK-cell percentage 5 days after the pregnancy termination could be a marker of immune aetiology of miscarriage, as the probability of an aborter with NK >12% to have an immune-mediated abortion is almost 90%.

In order to study the mechanism of abortion, the proportions of NK cells in the peripheral blood and decidual lymphocytes were evaluated in both chromosomally normal and abnormal missed abortions. In normal pregnancy, CD56+16-3- NK cells are a major element of decidual lymphocytes. The percentages of CD56+16-3-NK cells of peripheral lymphocytes in normal pregnancies were not statistically significantly different from those of chromosomally normal and abnormal abortions. In the decidua, the percentages of CD56+16-3- NK cells of decidual lymphocytes showed no statistically significant differences between normal pregnancies and chromosomally abnormal abortions. However, the percentages of CD56+16-3-NK cells of chromosomally normal abortions were lower than those of chromosomally abnormal (P = 0.0025). Moreover, the percentages of CD56+16- NK cells in abortions with normal chromosomes were lower than those in normal pregnancies or abortions with abnormal chromosomes (P = 0.0037, P = 0.0025). However, when the proportion of CD56+ NK cells expressing CD16 was evaluated, there were no statistically significant differences in the percentages of CD56+16+ NK cells in normal pregnancies and missed abortions with normal chromosomes and abnormal chromosomes. We conclude that the expression of decidual CD56+16-3- NK cells in missed abortions with normal chromosomes is different from abortions with abnormal chromosomes and that this phenomenon may depend on an abnormal immune response of the maternal side.