Deubiquitinase and unconjugated ubiquitin activate microenvironment inflammation and pain in eutopic and ectopic endometrium in endometriosis

В. А. Бурлев, N. A. Ilyasova
In: Russian Journal of Human Reproduction · 2023 · vol. 29(1) , pp. 9 · doi:10.17116/repro2023290119 · W4361803028
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Abstract

Background. It is known that deubiquitinasa and ubiquitin are important proteins that regulate inflammatory responses and metabolism of neuronal proteins by controlling the proteasomal pathway of their degradation. In addition, deubiquitinasa may be a biomarker of inflammation of neuronal origin. However, the role of deubiquitinasa and unconjugated ubiquitin as activators of microenvironment inflammation and pain in eutopic and ectopic endometrium in endometriosis has not been established. Objectives. To study the role of deubiquitinasa and unconjugated ubiquitin in eutopic and ectopic endometrium in patients with peritoneal endometriosis using immunohistochemical analysis, Western blotting, quantitative real-time polymerase chain reaction, enzyme immunoassay in blood and peritoneal fluid and compare these data with the presence of chronic pelvic pain. Method. Western blotting was used to quantify the content of conjugated and unconjugated ubiquitin in eutopic and ectopic endometrium in women with endometriosis. Immunohistochemical analysis was used to compare the results of ubiquitin expression in various cellular structures. Real-time quantitative polymerase chain reaction was used to assess ubiquitin gene expression. Determination of the concentration of ubiquitin in the peritoneal fluid and in the blood was carried out by enzyme immunoassay. All results were compared according to the presence or absence of chronic pelvic pain in relation to the control group. Results. In endometriosis in eutopic and ectopic endometrium, high levels of deubiquitinasa expression are observed, leading to the accumulation of unconjugated ubiquitin in the glands, which disrupts the process of proteasomal disintegration of proteins and affects the functional activity of the endometrium, namely the processes of pain induction. Conclusions. Overexpression of deubiquitinasa in microvessels and nerve fibers is combined with the expression of unconjugated ubiquitin in the epithelium of the glands and indicates a violation of the regulation of protein ubiquitinization in the endometrium due to the invasion of microvessels and nerve fibers. The determination of deubiquitinasa can serve as an indicator of the level of inflammation of the microenvironment in the endometrium to characterize the cause of pain.

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endometriosischronic_pelvic_pain

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