CORRELATIONS OF NLRP3 INFLAMMASOME mRNA GENES EXPRESSION LEVELS WITH THE STAGE OF ENDOMETRIOSIS IN WHOLE BLOOD OF WOMEN WITH ENDOMETRIOSIS ASSOCIATED WITH INFERTILITY

As you know, endometriosis is a chronic process that is accompanied by chronic pelvic pain. Currently, there is an ongoing discussion about non-invasive diagnostic markers. But there is still no single specific marker. The pathogenesis of chronic inflammation involves a progressive course, which is accompanied by long-term maintenance of the inflammasome in an active state due to excessive accumulation of intracellular and then extracellular DAMPs, their inefficient utilization by autophagy and stress-reducing cellular systems, local production of pro-inflammatory cytokines IL-1β, IL-18, and as well as the accumulation of M2 macrophages and helper T-lymphocytes of the 2nd type, tissue damage and the development of fibrosis. Regulation of IL-1 activity is carried out at two levels and requires the action of two stimulating signals – the first causes the expression of the inactive form of interleukins, proIL1α and proIL-1β, in which the active interleukin is connected to an additional peptide chain, which completely blocks the activity of proIL-1β and significantly to an extent - proIL-1α. The second level of regulation is carried out at the stage of activation of prointerleukins by proteolytic cleavage of the propeptide by the intracellular protease caspase-1, which is synthesized in the form of an inactive proenzyme The aim of the study. To study the gene expression levels of NLRP3 inflammasome and to determine the correlations between the exression levels of Nlrp3 inflammasome mRNA genes and the stages of endometriosis associated with infertility. Material and methods. To analyze the expression of NLRP3-inflammasome genes and to determine the relative normalized expression of NLRP3 mRNA, we used the polymerase chain reaction with real-time reverse transcription (RT-PCR) method in 50 women: 40 women with endometriosis and 10 women with tubal infertility. The object for molecular genetic studies by the RT-PCR method was the fraction of mononuclear cells isolated from the whole blood of patients with endometriosis. Statistical processing of the results of this section was carried out using non-parametric methods, namely the Wilcoxon-Mann-Whitney test, in which the indicators were considered reliable at p<0.05. Results. On the basis of the conducted study, it was established that the level of NLRP3-inflammasome mRNA expression in the blood of women with endometriosis associated with infertility is significantly increased compared to the indicators of the control group (44.43±3.72 u.u. and 0.85±0.03 u.o.) (р˂0.001). Such results of relative normalized expression of the NLRP3 gene turned out to be quite unexpected. It is obvious that such a high activation of the receptor is associated with the presence of potential ligands capable of activating it. Among the known objects with such ability and presence in the reproductive tract (endometrium) of women, a number of obligate and conditionally pathogenic microorganisms can be distinguished, which contain antigenic configurations (lipoproteins, peptidoglycan, glycolipids, zymosan of mushrooms) capable of activating NLRP3. However, opportunistic pathogens are not subject to mandatory drug elimination. However, it is not excluded that this very fact supports the growth of endometrioid ectopies with the help of mechanisms that are not fully understood. Conclusions: The level of NLRP3-inflammasome mRNA expression in the blood of women with endometriosis associated with infertility is significantly increased compared to the indicators of the control group (44.43±3.72 u.u. and 0.85±0.03 u.u.) (p˂0.001). Thus, increased expression of mRNA genes NLRP3 inflammasome, IL1β, HMGB1 in endometriosis can be considered as a protective reaction.