Role of macrophages in the immunopathogenesis of adenomyosis

Keywords: adenomyosis, menstrual disorder, pathophysiological mechanisms, immune regulation, macrophages, markers of phagocytic dysfunction, CD68 and CD163 cells

Abstract

The aim of the research: to study pathophysiological mechanisms of adenomyosis development by determining the role of macrophages in the uterine microenvironment.

Materials and methods: a prospective study has been conducted on 35 women. There were 20 (57.1 %) who had adenomyosis of I degree. The control group consisted of 15 (34.3 %) gynecologically healthy women. The patients underwent general clinical, instrumental (ultrasound, hysteroscopy) examinations. Fragments of the uterine wall obtained by hysterorectoscopy were used for morphological study. The method of immunohistochemical determination of CD68+ and CD163+ macrophages was used to analyze the characteristics of phenotypic equivalents of M1 and M2 macrophages in uterine tissue samples.

Results: The increase in the number of macrophages in the myometrium of patients with adenomyosis revealed in this study, which is found in large numbers in the areas of infiltration of the stroma of myometrial cells in close association with the perivascular region, can be regarded as the basis of the mechanism for the formation of endometrioid heterotopia. Furthermore, distortion of the CD68/CD163 ratio of macrophages is characterized by proinflammatory shift.

Conclusions: The study's main result is an increase in the quantitative indicators of CD68+ macrophages associated with adenomyosis, which indicates an immunopathological process in adenomyosis.

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Author Biographies

Nikolay Shcherbina, Kharkiv National Medical University

Department of Obstetrics and Gynecology No. 1

Anastasia Chekhunova, Kharkiv National Medical University

Department of Obstetrics and Gynecology No. 1

References

Burney, R. O., Giudice, L. C. (2012). Pathogenesis and pathophysiology of endometriosis. Fertility and Sterility, 98 (3), 511–519. doi: https://doi.org/10.1016/j.fertnstert.2012.06.029

Giudice, L. C., Kao, L. C. (2004). Endometriosis. The Lancet, 364 (9447), 1789–1799. doi: https://doi.org/10.1016/s0140-6736(04)17403-5

Kennedy, S., Bergqvist, A., Chapron, C., D’Hooghe, T., Dunselman, G., Greb, R. et. al. (2005). ESHRE guideline for the diagnosis and treatment of endometriosis. Human Reproduction, 20 (10), 2698–2704. doi: https://doi.org/10.1093/humrep/dei135

Laganà, A. S., Garzon, S., Götte, M., Viganò, P., Franchi, M., Ghezzi, F., Martin, D. C. (2019). The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights. International Journal of Molecular Sciences, 20 (22), 5615. doi: https://doi.org/10.3390/ijms20225615

Mehedintu, C., Plotogea, M. N., Ionescu, S., Antonovici, M. (2014). Endometriosis still a challenge. Journal of Medicine and Life, 7 (3), 349–357.

Adamson, G. D., Pasta, D. J. (2010). Endometriosis fertility index: the new, validated endometriosis staging system. Fertility and Sterility, 94 (5), 1609–1615. doi: https://doi.org/10.1016/j.fertnstert.2009.09.035

Amalinei, C., Păvăleanu, I., Lozneanu, L., Balan, R., Giuşcă, S.-E., Căruntu, I.-D. (2018). Endometriosis — insights into a multifaceted entity. Folia Histochemica et Cytobiologica, 56 (2), 61–82. doi: https://doi.org/10.5603/fhc.a2018.0013

Chapron, C., Marcellin, L., Borghese, B., Santulli, P. (2019). Rethinking mechanisms, diagnosis and management of endometriosis. Nature Reviews Endocrinology, 15 (11), 666–682. doi: https://doi.org/10.1038/s41574-019-0245-z

Zondervan, K. T., Becker, C. M., Koga, K., Missmer, S. A., Taylor, R. N., Viganò, P. (2018). Endometriosis. Nature Reviews Disease Primers, 4 (1). doi: https://doi.org/10.1038/s41572-018-0008-5

García-Gómez, E., Vázquez-Martínez, E. R., Reyes-Mayoral, C., Cruz-Orozco, O. P., Camacho-Arroyo, I., & Cerbón, M. (2020). Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis. Frontiers in Endocrinology, 10. doi: https://doi.org/10.3389/fendo.2019.00935

Maybin, J. A., Critchley, H. O. D. (2015). Menstrual physiology: implications for endometrial pathology and beyond. Human Reproduction Update, 21 (6), 748–761. doi: https://doi.org/10.1093/humupd/dmv038

Benagiano, G., Brosens, I., Habiba, M. (2013). Structural and molecular features of the endomyometrium in endometriosis and adenomyosis. Human Reproduction Update, 20 (3), 386–402. doi: https://doi.org/10.1093/humupd/dmt052

Matalliotakis, M., Zervou, M. I., Matalliotaki, C., Rahmioglu, N., Koumantakis, G., Kalogiannidis, I. et. al. (2017). The role of gene polymorphisms in endometriosis. Molecular Medicine Reports, 16 (5), 5881–5886. doi: https://doi.org/10.3892/mmr.2017.7398

Jerman, L. F., Hey-Cunningham, A. J. (2015). The Role of the Lymphatic System in Endometriosis: A Comprehensive Review of the Literature1. Biology of Reproduction, 92 (3). doi: https://doi.org/10.1095/biolreprod.114.124313

Sapkota, Y., Steinthorsdottir, V., Morris, A. P., Fassbender, A., Rahmioglu, N., De Vivo, I. et. al. (2017). Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism. Nature Communications, 8 (1). doi: https://doi.org/10.1038/ncomms15539

Thiruchelvam, U., Dransfield, I., Saunders, P. T. K., Critchley, H. O. D. (2012). The importance of the macrophage within the human endometrium. Journal of Leukocyte Biology, 93 (2), 217–225. doi: https://doi.org/10.1189/jlb.0712327

Hogg, C., Horne, A. W., Greaves, E. (2020). Endometriosis-Associated Macrophages: Origin, Phenotype, and Function. Frontiers in Endocrinology, 11. doi: https://doi.org/10.3389/fendo.2020.00007

Bonatz, G., Hansmann, M.-L., Buchholz, F., Mettler, L., Radzun, H. J., Semm, K. (1992). Macrophage- and lymphocyte-subtypes in the endometrium during different phases of the ovarian cycle. International Journal of Gynecology & Obstetrics, 37 (1), 29–36. doi: https://doi.org/10.1016/0020-7292(92)90974-n

Vallvé-Juanico, J., Santamaria, X., Vo, K. C., Houshdaran, S., Giudice, L. C. (2019). Macrophages display proinflammatory phenotypes in the eutopic endometrium of women with endometriosis with relevance to an infectious etiology of the disease. Fertility and Sterility, 112 (6), 1118–1128. doi: https://doi.org/10.1016/j.fertnstert.2019.08.060

Sekiguchi, K., Ito, Y., Hattori, K., Inoue, T., Hosono, K., Honda, M. et. al. (2019). VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues. Scientific Reports, 9 (1). doi: https://doi.org/10.1038/s41598-019-43185-8

Rőszer, T. (2015). Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms. Mediators of Inflammation, 2015, 1–16. doi: https://doi.org/10.1155/2015/816460

Wu, J., Xie, H., Yao, S., Liang, Y. (2017). Macrophage and nerve interaction in endometriosis. Journal of Neuroinflammation, 14 (1). doi: https://doi.org/10.1186/s12974-017-0828-3

Capobianco, A. (2013). Endometriosis, a disease of the macrophage. Frontiers in Immunology, 4. doi: https://doi.org/10.3389/fimmu.2013.00009

Atri, C., Guerfali, F., Laouini, D. (2018). Role of Human Macrophage Polarization in Inflammation during Infectious Diseases. International Journal of Molecular Sciences, 19 (6), 1801. doi: https://doi.org/10.3390/ijms19061801

Takebayashi, A., Kimura, F., Kishi, Y., Ishida, M., Takahashi, A., Yamanaka, A. et. al. (2014). Subpopulations of Macrophages within Eutopic Endometrium of Endometriosis Patients. American Journal of Reproductive Immunology, 73 (3), 221–231. doi: https://doi.org/10.1111/aji.12331

Kim, J., Bae, J.-S. (2016). Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment. Mediators of Inflammation, 2016, 1–11. doi: https://doi.org/10.1155/2016/6058147

Zhou, J., Tang, Z., Gao, S., Li, C., Feng, Y., Zhou, X. (2020). Tumor-Associated Macrophages: Recent Insights and Therapies. Frontiers in Oncology, 10. https://doi.org/10.3389/fonc.2020.00188

Amalinei, C., Păvăleanu, I., Lozneanu, L., Balan, R., Giuşcă, S.-E., Căruntu, I.-D. (2018). Endometriosis – insights into a multifaceted entity. Folia Histochemica et Cytobiologica, 56 (2), 61–82. doi: https://doi.org/10.5603/fhc.a2018.0013

Sun, H., Li, D., Yuan, M., Li, Q., Zhen, Q., Li, N., Wang, G. (2018). Macrophages alternatively activated by endometriosis-exosomes contribute to the development of lesions in mice. MHR: Basic Science of Reproductive Medicine, 25 (1), 5–16. doi: https://doi.org/10.1093/molehr/gay049

Role of macrophages in the immunopathogenesis of adenomyosis

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Published
2022-07-31
How to Cite
Shcherbina, N., & Chekhunova, A. (2022). Role of macrophages in the immunopathogenesis of adenomyosis. EUREKA: Health Sciences, (4), 50-56. https://doi.org/10.21303/2504-5679.2022.002644
Section
Medicine and Dentistry