Aseptic inflammation as the essential link in the pathogenesis of endometrioid disease




endometriosis, inducible NO-synthase, arginase 1, M1 phenotype macrophages, M2 phenotype macrophages


The paper was aimed at deter­mination of the quantitative activity of iNOS and Arg1, as well as M1 and M2 phenotype macrophages in women with endometrioid disease to establish their role in the pathogenesis of endometriosis. A prospective study was performed in gynecological units of the medical facilities of Poltava city. 140 women of reproductive age who made up the main group (110 women with endometrioid disease) and the control group (30 women without endometrioid disease) voluntarily participated in the study. All women underwent planned surgical treatment for existing gynecological pathology. Before surgical treatment, women were examined in accordance with the current Orders of the Ministry of Health of Ukraine. The spectrophotometric method was used to determine the enzymatic markers of macrophages (in the endometrium and peritoneal fluid) polarized into M1(iNOS) and M2 (Arg1) phenotypes. The type of macrophages was determined individually in each patient according to the ratios: in iNOS>Arg1, the M1 macrophage type prevailed; in Arg1>iNOS, the M2 macrophage type prevailed. When examining endometrial samplings in women from the main group, the iNOS indicator was by 1.4 times higher compared to women from the control group. The obtained results at the stage of entry into the abdominal cavity showed that mostly women from the main group suffered from the pelvic adhesion, especially stage 3 and stage 4. Among the obtained results, the increased quantitative activity in the peritoneal fluid of both iNOS and Arg1 in women of the main group was significant compared to the control group. When comparing the stages of endometrioid disease to the rates of quantitative activity of macrophage enzyme markers (in peritoneal fluid), it was found that the increase in the stage of the disease (from stage 3 to stage 4) caused an increase in the quantitative activity of Arg1 by 1.9 times and a decrease in the quantitative activity of iNOS by 2.9 times. Therefore, the planning of surgical intervention for women with endometrioid disease should consider a significant percentage of the pelvic adhesive disease, especially at the severe stages. Initiation of the chronic aseptic inflammatory process in endometrioid disease is caused by an increased quantitative activity of iNOS in the endometrium. In the pathogenesis of endometrioid disease, the presence of M2 phenotype macrophages in the peritoneal fluid is important, while the switching of macrophage phenotypes from a pro-inflammatory subpopulation to an anti-inflammatory one is crucial.


Zondervan KT, Becker CM, Missmer SA. Endo-metriosis. N Engl J Med. 2020 Mar 26;382(13):1244-56. doi:

de Freitas Fonseca M, Aragao LC, Sessa FV, Dutra de Resende JA Jr, Crispi CP. Interrelationships among endometriosis-related pain symptoms and their effects on health-related quality of life: a sectional observational study. Obstet Gynecol Sci. 2018 Sep;61(5):605-14. doi:

Hwang H, Chung YJ, Lee SR, Park HT, Song JY, Kim H, et al. Clinical evaluation and management of endo¬metriosis: guideline for Korean patients from Korean Society of Endometriosis. Obstet Gynecol Sci. 2018 Sep;61(5):553-64. doi:

Abd El–Kader AI, Gonied AS, Lotfy Moha-med M, Lotfy Mohamed S. Impact of endometriosis–related adhesions on quality of life among infertile women. Int J Fertil Steril. 2019 Apr;13(1):72-6. doi:

Mehdizadeh Kashi A, Moradi Y, Chaichian S, Najmi Z, Mansori K, Salehin F, et al. Application of the World Health Organization Quality of life instrument, short form (WHOQOL–BREF) to patients with endo-metriosis. Obstet Gynecol Sci. 2018 Sep;61(5):598-604. doi:

Likhachov VK, Shymanska YV, Savelieva YS, Vashchenko VL, Dobrovolska LМ. Changes of psycho-emotional state in the infertile pregnant females due to the anamnesis and IVF. Wiad Lek. 2019;72(4):562-7. doi:

1.Vallvé-Juanico J, Houshdaran S, Giudice LC. The endometrial immune environment of women with endometriosis. Human Reproduction Update [Internet]. 2019Jul.8;25(5):565-92. Available from:

Korchynska OO, Mashtepa AM, Voloshyna UV, Petrenko TG. [Endometriosis as one of contemporary problems in gynecology and obstetrics (analytical survey of scientific literature)]. Ukraina. Zdorovia natsii. 2015;2:104-15. Ukrainian.

Ramírez-Pavez TN, Martínez-Esparza M, Ruiz-Alcaraz AJ, Marín-Sánchez P, Machado-Linde F, García-Peñarrubia P. The Role of Peritoneal Macrophages in Endometriosis. Int J Mol Sci. 2021 Oct 6;22(19):10792. doi:

Orlova YuA, Hromova AM, Akimov OYe, Keto-va OM. [The role of the macrophage polarization type in the pathogenesis of endometrioid disease]. Zaporozhskyi medytsynskyi zhurnal. 2021;23(5):644-50. Ukrainian. doi:

de Campos GY, Oliveira RA, Oliveira-Brito PK, Roque-Barreira MC, da Silva TA. Pro-inflammatory res-ponse ensured by LPS and Pam3CSK4 in RAW 264.7 cells did not improve a fungistatic effect on Cryptococcus gattii infection. Peer J. 2020 Nov 25;8:e10295. doi:

Kumar S, Gupta E, Gupta N, Kaushik S, Srivas-tava VK, Kumar S, et al. Functional role of iNOS-Rac2 interaction in neutrophil extracellular traps (NETs) induced cytotoxicity in sepsis. Clin Chim Acta. 2021 Feb;513:43-9. doi:

Tanaka H, Kumasawa K, Kakigano A, Mimura K, Endo M, Tomimatsu T, et al. Arginase controls soluble vascular endothelial growth factor receptor 1 (sFlt1) to maintain pregnancy homeostasis. Biochem Biophys Res Commun. 2018 May 5;499(2):150-5. doi:

[On the approval and implementation of medical and technological documents on the standardization of medical care for genital endometriosis. Order of the Ministry of Health of Ukraine dated 2016 Apr 06 No. 319] [Internet]. 2016 [cited 2023 Apr 21]. Ukrainian. Available from:

Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022 Feb 26;2022(2):hoac009. doi:

Yadav G, Rao M, Gothwal M, Singh P, Kathuria P, Sharma PP. Detection of nerve fibers in the eutopic endometrium of women with endometriosis, uterine fib-roids and adenomyosis. Obstet Gynecol Sci. 2021 Sep;64(5):454-61. doi:

Skrypnyk I, Maslova G, Lymanets T, Gusachenko I. L-arginine is an effective medication for prevention of endothelial dysfunction, a predictor of anthracycline cardiotoxicity in patients with acute leukemia. Exp Oncol. 2017 Dec;39(4):308-11. doi:

Yelins’ka AM, Akimov OYe, Kostenko VO. Role of AP-1 transcriptional factor in development of oxidative and nitrosative stress in periodontal tissues during systemic inflammatory response. The Ukrainian Biochemical Journal. 2019;91(1):80-5. doi:

Akimov OYe, Kostenko VO. Role of NF-κB transcriptional factor activation during chronic fluoride intoxication in development of oxidative-nitrosative stress in rat’s gastric mucosa. Journal of Trace Elements in Medicine and Biology. 2020;61:126535. doi:

Akimov OYe, Kostenko VO. Functioning of nitric oxide cycle in gastric mucosa of rats under excessive combined intake of sodium nitrate and fluoride. The Ukrainian Biochemical Journal. 2016;88(6):70-5. doi:

Antomonov MYu. [Mathematical processing and analysis of biomedical data]. Kyiv: Medinform; 2018. 579 p. Russian.

The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, 201 mul-lerian anomalies and intrauterine adhesions. Fertil Steril. 1988 Jun;49(6):944-55. doi:

Burns KA, Thomas SY, Hamilton KJ, Young SL, Cook DN, Korach KS. Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk. Endocrinology. 2018 Jan 1;159(1):103-18. doi:

Tanbo T, Fedorcsak P. Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options. Acta Obstet Gynecol Scand. 2017 Jun;96(6):659-67. doi:

Suschek CV, Schnorr O, Kolb-Bachofen V. The role of iNOS in chronic inflammatory processes in vivo: is it damage-promoting, protective, or active at all? Curr Mol Med. 2004 Nov;4(7):763-75. doi:

Kvaskoff M, Mahamat-Saleh Y, Farland LV, Shigesi N, Terry KL, Harris HR, et al. Endometriosis and cancer: a systematic review and meta-analysis. Hum Reprod Update. 2021 Feb 19;27(2):393-420. doi:

Kielbik M, Szulc-Kielbik I, Klink M. The Potential Role of iNOS in Ovarian Cancer Progression and Chemoresistance. Int J Mol Sci. 2019 Apr 9;20(7):1751. doi:




How to Cite

Orlova Y, Hromova A, Ketova O, Liakhovska T, Martynenko V, Krutikova E. Aseptic inflammation as the essential link in the pathogenesis of endometrioid disease. Med. perspekt. [Internet]. 2023Sep.29 [cited 2024Mar.3];28(3):55-61. Available from: