The role of the macrophage polarization type in the pathogenesis of endometrioid disease

In: Zaporozhye Medical Journal · 2021 · vol. 23(5) , pp. 644–650 · doi:10.14739/2310-1210.2021.5.233689 · W3211440450
article OA: diamond CC0 ⤵ 1 in-corpus citation
AI-generated summary by claude@2026-06, 2026-06-07

This study quantified macrophage polarization in women with and without endometrioid disease, finding a higher prevalence of the M2 phenotype in the peritoneal fluid of affected individuals, suggesting its role in disease pathogenesis.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text

This study examined macrophage polarization (M1 vs M2) by comparing iNos and Arg1 marker enzyme activities in endometrial samples and peritoneal fluid from 50 women with endometrioid disease and 30 controls without such disease, including evaluation of pelvic adhesions and disease severity. Using spectrophotometric assessment of iNos/Arg1 activity ratios, the authors found a higher proportion of M2-polarized macrophages in peritoneal fluid in the endometrioid disease group (58.3% vs 28.6%) and reported that M2 polarization was associated with greater severity, especially stage/degree 4; mean iNOS activity was also increased in both peritoneal fluid and endometrium in the main group (about 1.7-fold). The paper’s main limitation is the relatively small sample size and reliance on a polarization definition based on enzyme activity ratios rather than direct macrophage functional profiling. This paper is centrally about endometriosis — it investigates M1/M2 macrophage polarization and iNOS/Arg1 activity in endometrioid disease and links M2 polarization to disease development and severity.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

Endometriosis today occupies one of the leading places in the structure of general gynecological pathology. Theories of the onset and progression of this disease are controversial. One of the most widespread theories is the assumption that endometriosis is a disease of macrophages. The question of which the macrophage phenotype, M1 or M2, is the leading one, however, remains controversial. The aim. To determine the type of macrophage polarization (M1/M2) and the quantitative activity of their marker enzymes (iNos/Arg1) in the endometrium and peritoneal fluid in endometrioid disease. Materials and methods. The total number of reproductive age (30.95±6.49) women enrolled in the study was 80. The main group consisted of 50 women with endometrioid disease. The control group included 30 women without signs of endometrioid disease. Women from the main group (n=24) and the control group (n=27) underwent endometrial sampling using an intrauterine Pipelle catheter in the first phase of the menstrual cycle before a surgery. During laparoscopic or laparotomy approaches, peritoneal fluid was taken (in the main group n=24, in the control group n=28). The type of macrophage polarization (M1 or M2) was determined based on the ratio of marker enzymes (Arg1, iNos) activity in each patient using a spectrophotometric method in the endometrium and peritoneal fluid. The polarization to the M1 phenotype was determined at iNos>Arg1, and at Arg1>iNos– the polarization to the M2 phenotype. Results. As a result of the study, it was revealed that in women with endometrioid disease, pelvic adhesions were much more common, 84.0% versus 46.7% in women without it, and especially 3 and 4 degree of severity (P<0.05). When assessing the type of macrophages in the peritoneal fluid, a significantly greater number of the main group women had the M2 phenotype of macrophage polarization compared to the control group (58.3% versus 28.6%, P=0.03). It was the macrophage polarization to the M2 phenotype that influenced the severity of endometrioid disease, especially the 4 degree of severity. The mean values of the iNOS activity in the main group women, both in the peritoneal fluid and in the endometrium, significantly differed from those in the control group patients (by 1.73 and 1.77 times, respectively). Conclusions. Thus, we can conclude that endometriosis is a disease, the development and progression of which is induced by the M2 phenotype of macrophages. Considering the increase in the mean levels of iNOS activity both in the peritoneal fluid and in the endometrium, it can be concluded that iNOS influences the pathogenesis of endometrioid disease.
Full text 10,770 characters · extracted from oa-doi-fallback · 2 sections · click to expand

Materials

and methods. The total number of reproductive age (30.95±6.49) women enrolled in the study was 80. The main group consisted of 50 women with endometrioid disease. The control group included 30 women without signs of endometrioid disease. Women from the main group (n=24) and the control group (n=27) underwent endometrial sampling using an intrauterine Pipelle catheter in the first phase of the menstrual cycle before a surgery. During laparoscopic or laparotomy approaches, peritoneal fluid was taken (in the main group n=24, in the control group n=28). The type of macrophage polarization (M1 or M2) was determined based on the ratio of marker enzymes (Arg1, iNos) activity in each patient using a spectrophotometric method in the endometrium and peritoneal fluid. The polarization to the M1 phenotype was determined at iNos>Arg1, and at Arg1>iNos– the polarization to the M2 phenotype. Results. As a result of the study, it was revealed that in women with endometrioid disease, pelvic adhesions were much more common, 84.0% versus 46.7% in women without it, and especially 3 and 4 degree of severity (P<0.05). When assessing the type of macrophages in the peritoneal fluid, a significantly greater number of the main group women had the M2 phenotype of macrophage polarization compared to the control group (58.3% versus 28.6%, P=0.03). It was the macrophage polarization to the M2 phenotype that influenced the severity of endometrioid disease, especially the 4 degree of severity. The mean values of the iNOS activity in the main group women, both in the peritoneal fluid and in the endometrium, significantly differed from those in the control group patients (by 1.73 and 1.77 times, respectively). Conclusions. Thus, we can conclude that endometriosis is a disease, the development and progression of which is induced by the M2 phenotype of macrophages. Considering the increase in the mean levels of iNOS activity both in the peritoneal fluid and in the endometrium, it can be concluded that iNOS influences the pathogenesis of endometrioid disease.

References

- Pshenichnyuk, E. Yu., Asaturova, A. V., Adamyan, L. V., & Zaitsev, N. V. (2018). Immunogistokhimicheskie osobennosti eutopicheskogo i ektopicheskogo endometriya u patsientok s retsidiviruyushchim techeniem endometrioidnykh kist yaichnikov [Immunohistochemical features of eutopic and ectopic endometrium in patients with recurrent ovarian endometrioid cysts]. Akusherstvo i ginekologiya, (3), 84-95. https://doi.org/10.18565/aig.2018.3.84-95 [in Russian]. - Baranov, V. S. (2013). Endometrioz kak problema sistemnoi genetiki [Endometriosis as systemic genetic problem]. Zhurnal akusherstva i zhenskikh boleznei, 62(1), 71-78. https://doi.org/10.17816/JOWD62171-78 [in Russian]. - Wang, Y., Nicholes, K., & Shih, I. M. (2020). The Origin and Pathogenesis of Endometriosis. Annual Review of Pathology: Mechanisms of Disease, 15, 71-95. https://doi.org/10.1146/annurev-pathmechdis-012419-032654 - Sokolov, D. I., Kondratjeva, P. G., Jarmolinskaja, M. I., Kramareva, N. L., Seljutin, A. V., Rulev, V. V, Niauri, D. A. & Selkov, S. A. (2014). Soderzhanie khemokinov i tsitokinov v peritoneal'noi zhidkosti bol'nykh naruzhnym genital'nym endometriozom razlichnoi stepeni tyazhesti [Contents of chemokines and cytokines in peritoneal fluid from the patients with endometriosis of various severity]. Meditsinskaya immunologiya, 9(1), 85-90. https://doi.org/10.15789/1563-0625-2007-1-85-90 [in Russian]. - Wu, J., Xie, H., Yao, S., & Liang, Y. (2017). Macrophage and nerve interaction in endometriosis. Journal of Neuroinflammation, 14(1), Article 53. https://doi.org/10.1186/s12974-017-0828-3 - Monastyrskaya, E. A., Lyamina, S. V., & Malyshev, I. Yu. (2008). M1 i M2 fenotipy aktivirovannykh makrofagov i ikh rol' v immunnom otvete i patologii [Ml and М2 phenotypes of activated macrophages and their role in immune response and pathology]. Patogenez, 6(4), 31-39. [in Russian]. - Ponomarenko, I. V., Koneva, O. A., & Altukhova, O. B. (2016). Molekulyarnye osnovy etiopatogeneza i kliniki endometrioza [Molecular basis of pathogenesis and clinical endometriosis]. Nauchnye vedomosti Belgorodskogo gosudarstvennogo universiteta. Seriya: Meditsina. Farmatsiya, (19), 11-16. [in Russian]. - Podgaec, S., Dias Junior, J. A., Chapron, C., Oliveira, R. M., Baracat, E. C., & Abrão, M. S. (2010). Th1 and Th2 ummune responses related to pelvic endometriosis. Revista da Associação Médica Brasileira, 56(1), 92-98. https://doi.org/10.1590/s0104-42302010000100022 - de Campos, G. Y., Oliveira, R. A., Oliveira-Brito, P., Roque-Barreira, M. C., & da Silva, T. A. (2020). Pro-inflammatory response ensured by LPS and Pam3CSK4 in RAW 264.7 cells did not improve a fungistatic effect on Cryptococcus gattii infection. PeerJ, 8, Article e10295. https://doi.org/10.7717/peerj.10295 - Kumar, S., Gupta, E., Gupta, N., Kaushik, S., Srivastava, V. K., Kumar, S., Mehta, S., & Jyoti, A. (2021). Functional role of iNOS-Rac2 interaction in neutrophil extracellular traps (NETs) induced cytotoxicity in sepsis. Clinica Chimica Acta, 513, 43-49. https://doi.org/10.1016/j.cca.2020.12.004 - Ministry of Health of Ukraine. (2006, April 06). Pro zatverdzhennia ta vprovadzhennia medyko-tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry henitalnomu endometriozi [On Approval and implementation of the medical and technological documents on standardizing the management of genital endometriosis (No. 319)]. https://www.dec.gov.ua/mtd/genitalnyj-endometrioz/ - Yelins’ka, A. M., Akimov, O. Ye., & Kostenko, V. O. (2019). Role of AP-1 transcriptional factor in development of oxidative and nitrosative stress in periodontal tissues during systemic inflammatory response. The Ukrainian Biochemical Journal, 91(1), 80-85. https://doi.org/10.15407/ubj91.01.080 - Akimov, O. Ye., & Kostenko, V. O. (2020). 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, 61, Article 126535. https://doi.org/10.1016/j.jtemb.2020.126535 - Akimov, O. Ye., & Kostenko, V. O. (2016). Functioning of nitric oxide cycle in gastric mucosa of rats under excessive combined intake of sodium nitrate and fluoride. The Ukrainian Biochemical Journal, 88(6), 70-75. https://doi.org/10.15407/ubj88.06.070 - Zakharov, I. S., Ushakova, G. A., Demyanova, T. N., Bolotova, S. N., Fetischeva, L. E., Petrich, L. N. & Dodonova, G. H. (2016). Spaechnaya bolezn' organov malogo taza: sovremennye vozmozhnosti profilaktiki [Adhesive disease of the pelvic organs: modern prevention opportunities]. Consilium Medicum, 18(6), 71-73. https://doi.org/10.26442/2075-1753_2016.6.71-73 [in Russian]. - Working group of ESGE, ESHRE and WES, Saridogan, E., Becker, C. M., Feki, A., Grimbizis, G. F., Hummelshoj, L., Keckstein, J., Nisolle, M., Tanos, V., Ulrich, U. A., Vermeulen, N., & De Wilde, R. L. (2017). Recommendations for the Surgical Treatment of Endometriosis. Part 1: Ovarian Endometrioma. Human Reproduction Open, 2017(4), Article hox016. https://doi.org/10.1093/hropen/hox016 - Miller, J. E., Ahn, S. H., Marks, R. M., Monsanto, S. P., Fazleabas, A. T., Koti, M., & Tayade, C. (2020). IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis. Frontiers in Immunology, 11, Article 108. https://doi.org/10.3389/fimmu.2020.00108 - Burns, K. A., Thomas, S. Y., Hamilton, K. J., Young, S. L., Cook, D. N., & Korach, K. S. (2018). Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk. Endocrinology, 159(1), 103-118. https://doi.org/10.1210/en.2017-00562 - Hudson, Q. J., Ashjaei, K., Perricos, A., Kuessel, L., Husslein, H., Wenzl, R., & Yotova, I. (2020). Endometriosis Patients Show an Increased M2 Response in the Peritoneal CD14+low/CD68+low. Macrophage Subpopulation Coupled with an Increase in the T-helper 2 and T-regulatory Cells. Reproductive Sciences, 27(10), 1920-1931. https://doi.org/10.1007/s43032-020-00211-9 - Shamarakova, M. V., Adamyan, L. V., Asaturova, A. V., Ezhova, L. S., Zaitsev, N. V., Yurova, M. V., & Martirosyan, Ya. O. (2018). Seromutsinoznye opukholi yaichnikov i endometrioz u zhenshchin reproduktivnogo vozrasta [Seromucinous ovarian tumors and endometriosis in reproductive-aged women]. Akusherstvo i ginekologiya, (7), 84-91. https://doi.org/10.18565/aig.2018.7.84-91 [in Russian]. - Kielbik, M., Szulc-Kielbik, I., & Klink, M. (2019). The Potential Role of iNOS in Ovarian Cancer Progression and Chemoresistance. International Journal of Molecular Sciences, 20(7), Article 1751. https://doi.org/10.3390/ijms20071751 - Yeo, S. G., Won, Y. S., Lee, H. Y., Kim, Y. I., Lee, J. W., & Park, D. C. (2013). Increased Expression of Pattern Recognition Receptors and Nitric Oxide Synthase in Patients with Endometriosis. International Journal of Medical Sciences, 10(9), 1199-1208. https://doi.org/10.7150/ijms.5169 - Yu, J., Chen, L. H., Zhang, B., & Zheng, Q. M. (2019). The modulation of endometriosis by lncRNA MALAT1 via NF-κB/iNOS. European Review for Medical and Pharmacological Sciences, 23(10), 4073-4080. https://doi.org/10.26355/eurrev_201905_17908 - Dhall, S., Coksaygan, T., Hoffman, T., Moorman, M., Lerch, A., Kuang, J. Q., Sathyamoorthy, M., & Danilkovitch, A. (2018). Viable cryopreserved umbilical tissue (vCUT) reduces post-operative adhesions in a rabbit abdominal adhesion model. Bioactive Materials, 4(1), 97-106. https://doi.org/10.1016/j.bioactmat.2018.09.002 Downloads Published How to Cite Issue Section License Authors who publish with this journal agree to the following terms: Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (22)

Cited by (1)

Source provenance

openalex
last seen: 2026-06-10T17:14:06.276822+00:00
License: CC0 · commercial use OK