{"paper_id":"dd9dafcf-e7e3-4265-8e49-0035e2a38342","body_text":"RELATIONSHIPS BETWEEN THE EXPRESSION LEVELS OF NLRP3-INFLAMMASOME, IL-1Β, HMGB1 IN THE BLOOD OF WOMEN WITH ENDOMETRIOSIS ASSOCIATED WITH INFERTILITY DEPENDING ON THE STAGES OF ENDOMETRIOSIS\nAbstract\nIntroduction. The exact role of HMGB1 in the development of endometriosis is not fully understood. HMGB1 (high mobility group box) is a family of chromosomal proteins of the high mobility group, consisting of non-histone chromosomal proteins widely distributed in eukaryotic cells. HMGB1 is stably localized in the cell nucleus under normal physiological conditions (it is a nuclear protein); however, under conditions of oxidation or inflammation, it is released from the nucleus into the cytoplasm, and then secreted into the extracellular matrix through the process of exocytosis. It has been proven that HMGB1, TLR-4-mediated inflammatory signalling system is involved in the formation of multiple tumor inflammatory pathological microenvironments and participates in inflammatory tumor proliferation, invasion and metastasis and other pathological mechanisms. Nevertheless, the role of HMGB1 in the formation of the pathological inflammatory microenvironment of endometriosis remains unclear.\nIn 2002, the study of molecular mechanisms of chronification of the inflammatory process made it possible to discover inflammasomes – new markers of normal and pathological inflammatory reactions that regulate the functional activity of effector cells. In the course of research, it was proved that the activation of specific molecular structures precedes any inflammatory reaction. Inflammasomes – members of the family of cytosolic NOD (nucleotide-binding and oligomerization domains) -like receptors (NOD-like receptors, NLR) – are a multi-protein oligomeric complex responsible for the activation of the inflammatory response, promote the maturation and secretion of pro-inflammatory cytokines interleukin-1β (IL- 1β), the secretion of which causes pyroptosis – a special type of programmed cell death.\nThe aim of the study: to investigate the relationships between the expression levels of NLRP3-inflammasome, IL-1Β, HMGB1 in the whole blood of women with endometriosis associated with infertility depending on the stages of endometriosis.\nMaterials and methods. To analyze the expression of NLRP3-inflammasome, IL-1β, HMGB1 genes and to determine the relative normalized expression of NLRP3, IL-1β, HMGB1 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.\nStatistical processing of the results of this section was carried out using non-parametric methods, namely the Wilcoxon-Mann-Whitney test, in which indicators were considered reliable at p<0.05.\nResults. The results of the NLRP3-inflammasome expression levels obtained by us indicate its growth, so the next stage of our research was to determine the NLRP3-inflammasome expression levels depending on the stages of endometriosis. At the same time, it was established that in the group of women without clinical symptoms (according to the classification of rASF, 1997 – these are women with stage 1 and 2 of endometriosis) – in 20 women, the level of expression of NLRP3-inflammasome is 10.07±1.18 c.u. With the progression of the disease, there is an increase in the indicator from 26.59±1.83 c.u. – in 12 women with middle-stage endometriosis up to 50.08± 3.26 c.u. – in 8 women with severe stage endometriosis. At the same time, the presence of a probable difference between all indicators was established (p<0.001).\nOur results of IL-1β expression levels, as well as NLRP3-inflammasome expression, indicate its growth depending on the stages of endometriosis: in 20 women, the level of IL-1β expression is 3.74±0.18 units, in 12 women – 14.3±0.73 c.u., in 8 women – 65.02±3.26 c.u. At the same time, the presence of a probable difference between all indicators was similarly established (p <0.001).\nAs a result of the work, an increase in expression levels was established HMGB1 that is why we determined the expression levels HMGB1, depending on the stages of endometriosis: expression level in 20 womenHMGB1is 4.76±0.22 c.u. With the progression of the disease, there is an increase in the indicator from 9.94±0.73 – in 12 women with endometriosis of the middle stage to 22.97±1.23 – in 8 women with endometriosis of a severe stage.\nAt the same time, the presence of a probable difference between all indicators was established (p<0.001).\nConclusion. We investigated the relationships between the expression levels of NLRP3 inflammasome, IL-1β, HMGB1 in the blood of women with endometriosis associated with infertility depending on the stages of endometriosis. In the blood of women with endometriosis associated with infertility, a significant increase in the expression of NLRP3-inflammasome, IL-1β, HMGB1 was established (p<0,001) depending on the stages of endometriosis directly proportional dependence with the progression of the disease.\nDownloads\nReferences\nFan D, Wang X, Shi Z, Jiang Y, Zheng B, Xu L, et al. Understanding endometriosis from an immunomicroenvironmental perspective. Chin Med J (Engl). 2023;136(16):1897-909. doi: 10.1097/CM9.0000000000002649\nHogg C, Horne AW, Greaves E. Endometriosis-Associated Macrophages: Origin, Phenotype, and Function. Front Endocrinol (Lausanne). 2020;11:1-15. doi: 10.3389/fendo.2020.00007\nMa C, Huang W, Wang H, Yao W, Liang M, Yu G, et al. Oxidized LDL promotes EMS-induced angiogenesis by increasing VEGF-A expression and secretion by endometrial cells. Mol Med. 2022;28(1):1-13. doi: 10.1186/s10020-022-00582-6\nБігун РВ, Геник НІ, Крижанівська АЄ, Дзьомбак ВБ, Гаврилюк ГМ, Островська ОМ. 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