Macrophage cell populations in infertile women
Merkulov E.D., Svarovsky D.A., Samoilova Yu.G., Spirina L.V., Stakheeva M.N., Okkel Yu.V., Sidorenkova K.A., Petrov I.A., Prozorova A.V., Sulim V.V., Ulyanova A.S., Kubykina M.I., Arkhipova Ya.I.
Infertility remains a major medical and social challenge that affects a substantial proportion of the reproductive-age population. One of the factors influencing the outcome of in vitro fertilization (IVF) is the status of the immune microenvironment and phenotypic plasticity of macrophages involved in the regulation of inflammation, implantation, and early embryonic development.
Objective. To investigate the phenotypic characteristics of in vitro-induced peripheral blood macrophages in infertile women, their responsiveness to polarizing stimuli (lipopolysaccharide [LPS] and IL-4), and their association with embryo quality in IVF cycles.
Materials and methods. This study included women with various forms of infertility who underwent IVF. Lipopolysaccharide (LPS) and interleukin (IL)-4 were used to induce macrophage activation. The CD68+HLA-DR+CD80+/- and CD68+CD163+/-CD206+/- macrophage subpopulations were analyzed using flow cytometry. The concentration of tumor necrosis factor alpha (TNF-α) in the cell culture supernatants was determined using an enzyme-linked immunosorbent assay (ELISA).
Results. Poor embryo quality was associated with a predominance of incompletely activated CD68+HLA-DR+CD80− macrophages, whereas high embryo quality was associated with increased proportions of both classical M1 macrophages (CD68+HLA-DR+CD80+) and alternatively activated CD68+CD163−CD206+ macrophages. TNF-α concentrations reached their highest levels following LPS stimulation, with the highest values observed in women with excellent-quality embryos. Anovulatory infertility was characterized by a significantly higher proportion of CD68+HLA-DR−CD80+ macrophages than in other infertility subtypes. Correlation analysis confirmed the existence of a continuum of macrophage polarization, reflecting the balance between mature and immature macrophage subpopulations.
Conclusion. The phenotypic composition and functional responsiveness of macrophages are closely associated with embryo quality during IVF. The identified characteristics define an immunological profile with prognostic potential and may serve as the basis for personalized approaches to infertility treatment.
Authors' contributions. Merkulov E.D., Svarovsky D.A. – conception and design of the study, data analysis and interpretation; Spirina L.V., Stakheeva M.N. – scientific supervision, methodological support, writing and editing of the article;
Samoilova Yu.G., Okkel Yu.V., Petrov I.A. – clinical support of the study, formation of patient groups, analysis of clinical data; Sulim V.V., Ulyanova A.S. – experimental studies, cell culture management; Sidorenkova K.A., Prozorova A.V., Kubykina M.I., Arkhipova Ya.I. – collection of clinical and laboratory material, systematization of clinical and embryological data. All authors approved the final version of the manuscript prior to publication and agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part are appropriately investigated and resolved.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: The study was conducted with financial support from the Siberian State Medical University of the Ministry of Health.
Ethical approval: The study was reviewed and approved by the Research Ethics Committee of the Siberian State Medical University of the Ministry of Health (Ref. No: 8 of 18.01.2023).
Use of generative artificial intelligence: No artificial intelligence tools were used in the preparation of this manuscript.
Patient consent for publication: All patients provided informed consent for the publication of their data.
Authors' data sharing statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Merkulov E.D., Svarovsky D.A., Samoilova Yu.G., Spirina L.V., Stakheeva M.N., Okkel Yu.V.,
Sidorenkova K.A., Petrov I.A., Prozorova A.V., Sulim V.V., Ulyanova A.S., Kubykina M.I., Arkhipova Ya.I.
Macrophage cell populations in infertile women.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (7): 114-134 (in Russian):
https://dx.doi.org/10.18565/aig.2025.291
Keywords
follicular fluid
macrophages
monocytes
embryos
cytokines
IVF
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Received 16.10.2025
Accepted 15.06.2026
About the Authors
Evgeny D. Merkulov, PhD student at the Department of Biochemistry and Molecular Biology with a course of clinical laboratory diagnostic, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, evmerc@mail.ru, https://orcid.org/0000-0002-7082-9389Dmitry A. Svarovsky, Teaching Assistant at the Department of Biochemistry and Molecular Biology with a course of clinical laboratory diagnostic, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2; PhD student, Cancer Research Institute Tomsk NRMC, 634009, Russia, Tomsk, Cooperative lane, 5, svarovsky.d.a@gmail.com, Scopus AuthorID: 57417248900; eLibrary SPIN: 4131-8608, https://orcid.org/0000-0002-8985-009X
Iuliia G. Samoilova, Dr. Med. Sci., Рrofessor, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2; Director of the Institute of Medicine and Medical Technologies, Novosibirsk National Research State University, +7(913)826-74-24, samoilova_y@inbox.ru,
https://orcid.org/0000-0002-2667-4842
Liudmila V. Spirina, Dr. Med. Sci., Head of the Department of Biochemistry and Molecular Biology with a course of clinical laboratory diagnostics, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, spirinalvl@mail.ru, https://orcid.org/0000-0002-5269-736X
Marina N. Stakheeva, Dr. Med. Sci., Professor, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2; Leading Researcher at the Laboratory of Molecular Oncology and Immunology, Cancer Research Institute Tomsk NRMC, 634009, Russia, Tomsk, Cooperative lane, 5,
stakheyevam@oncology.tomsk.ru, https://orcid.org/0000-0003-0601-2240
Iuliia V. Okkel, PhD, Teaching Assistant, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, okkel_uv@mail.ru, https://orcid.org/0000-0001-6386-1535
Kira A. Sidorenkova, PhD student at the Department of Obstetrics and Gynecology, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, +7(952)884-37-49, kirasidorenkova@mail.ru, https://orcid.org/0009-0007-6263-6716
Ilya A. Petrov, Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, +7(952)899-83-66, obgynsib@gmail.com, https://orcid.org/0000-0002-0697-3896
Victoria V. Sulim, 4 year student, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, vinnnnnnyy@gmail.com, https://orcid.org/0009-0007-9099-6268
Anna S. Ulyanova, 4 year student, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, anna.ulnv0204@gmail.com, https://orcid.org/0009-0004-9313-0791
Marina I. Kubykina, obstetrician-gynecologist, reproductologist at the ART Center, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, marina.kubykina@mail.ru, https://orcid.org/0009-0002-4598-1079
Yana I. Arkhipova, obstetrician-gynecologist, reproductologist at the ART Center, Siberian State Medical University, Ministry of Health of Russia, 634050, Russia, Tomsk, Moscowski Trakt str., 2, yana_98@icloud.com, https://orcid.org/0009-0002-1062-7344
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