Prognostic significance of CD68+macrophages in autoimmune inflammation in experimental study

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Abstract

Introduction. Autoimmune oophoritis is one of the causes of premature ovarian insufficiency in 3–40% of cases. Representative diagnosis is possible only through histological examination of ovarian biopsy material, which complicates the identification of early stages of the pathological process when changes may be reversible.

Objective: to study the number and localization of antigen-presenting cells (macrophages) expressing CD68 and determine their role in the pathogenesis of autoimmune inflammation during the formation of experimental autoimmune oophoritis and experimental bacterial chronic inflammation of uterine appendages.

Material and methods. The study was conducted on 45 mature outbred female rats divided into 3 groups: main group with autoimmune oophoritis model (n=25), comparison group with bacterial chronic inflammation of uterine appendages model (n=10), and control group (n=10). Histological examination of ovaries, immunohistochemical staining with CD68 antibodies, and determination of anti-ovarian antibodies in blood serum were performed.

Results. In autoimmune oophoritis, high CD68 expression was revealed on the surface of M1 phenotype tissue macrophages. Maximum numerical density of CD68+macrophages was reached by day 15 of the experiment (714.62 cells/mm2), while in bacterial inflammation by day 60 (492.84 cells/mm2). CD68+macrophages migrate from medulla to cortex, surrounding growing follicles. By day 30, a decrease in the number of growing follicles and an increase in atretic bodies were noted with elevated anti-ovarian antibody concentrations to 10.3–14.1 ng/ml.

Conclusion. Macrophages with increased CD68+expression may serve as promising early markers of premature ovarian insufficiency of autoimmune etiology, which is of interest for clinical practice.

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About the authors

Margarita Leonidovna Dmitrieva

FSFEI HE “Siberian State Medical University” of the Ministry of Health of the Russian Federation

Author for correspondence.
Email: dmitrieva.ml@ssmu.ru
ORCID iD: 0000-0002-2958-9424
SPIN-code: 3312-5500

Candidate of Medical Sciences, Associate Professor, Associate Professor of the Department of Obstetrics and Gynecology

Russian Federation, Moskovsky tract, 2, Tomsk, 634050

Olga Anatolyevna Tikhonovskaya

FSFEI HE “Siberian State Medical University” of the Ministry of Health of the Russian Federation

Email: tikhonovskaya.oa@ssmu.ru
ORCID iD: 0000-0003-4309-5831
SPIN-code: 2458-0890

Doctor of Medical Sciences, Professor of the Department of Obstetrics and Gynecology

Russian Federation, Moskovsky tract, 2, Tomsk, 634050

Sergey Valentinovich Logvinov

FSFEI HE “Siberian State Medical University” of the Ministry of Health of the Russian Federation

Email: logvinov.sv@ssmu.ru
ORCID iD: 0000-0002-9876-6957
SPIN-code: 3998-9015

Doctor of Medical Sciences, Professor, Head of the Department of Histology, Embryology and Cytology

Russian Federation, Moskovsky tract, 2, Tomsk, 634050

Liliya Ramilyevna Mustafina

FSFEI HE “Siberian State Medical University” of the Ministry of Health of the Russian Federation

Email: lrmustafina@yandex.ru
ORCID iD: 0000-0003-3526-7875
SPIN-code: 1070-7905

Doctor of Medical Sciences, Professor of the Department of Histology, Embryology and Cytology

Russian Federation, Moskovsky tract, 2, Tomsk, 634050, Russian Federation

Ilya Alekseevich Petrov

FSFEI HE “Siberian State Medical University” of the Ministry of Health of the Russian Federation

Email: petrov.ia@ssmu.ru
ORCID iD: 0000-0002-0697-3896
SPIN-code: 8356-5503

Doctor of Medical Sciences, Professor of the Department of Obstetrics and Gynecology, Head of the Assisted Reproductive Technologies Center

Russian Federation, Moskovsky tract, 2, Tomsk, 634050

Ekaterina Grigor’evna Bordunova

FSFEI HE “Siberian State Medical University” of the Ministry of Health of the Russian Federation

Email: katabordunova6@gmail.com
ORCID iD: 0009-0001-6951-9391

3th year student of the pediatric faculty

Russian Federation, Moskovsky tract, 2, Tomsk, 634050

Iuliia Gennadievna Samoilova

FSFEI HE “Siberian State Medical University” of the Ministry of Health of the Russian Federation; Novosibirsk National Research State University

Email: samoilova_y@inbox.ru
ORCID iD: 0000-0002-2667-4842
SPIN-code: 8644-8043

Doctor of Medical Sciences, Professor of the Department of Faculty Therapy with Clinical Pharmacology Course, Head of the Department of Pediatrics with Endocrinology Course, Director of the Institute of Medicine and Medical Technologies

Russian Federation, Moskovsky tract, 2, Tomsk, 634050; Pirogova str., 1, Novosibirsk, 630090

Dmitry Anatolyevich Kudlay

Novosibirsk National Research State University; Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); National Research Center – Institute of Immunology Federal Medical-Biological Agency of Russia

Email: dakudlay@generium.ru
ORCID iD: 0000-0003-1878-4467
SPIN-code: 4129-7880

Doctor of Medical Sciences, Corresponding Member of the Russian Academy of Sciences, Director of Innovative Development Programs, Professor, Department of Pharmacology at the Institute of Pharmacy, Leading Researcher, Laboratory of Personalized Medicine and Molecular Immunology No.71

Russian Federation, Pirogova str., 1, Novosibirsk, 630090; Trubetskaya st., 8, build. 2, Moscow, 119991; Kashirskoe shosse, 24, Moscow, 115522

References

  1. Komorowska B. Autoimmune premature ovarian failure. Prz Menopauzalny. 2016; 15 (4): 210–4. doi: 10.5114/pm.2016.65666
  2. Wang Y., Jiang J., Zhang J., Fan P., Xu J. Research Progress on the Etiology and Treatment of Premature Ovarian Insufficiency. Biomed Hub. 2023; 8 (1): 97–107. doi: 10.1159/000535508
  3. Bakalov V.K., Anasti J.N., Calis K.A., Vanderhoof V.H., Premkumar A., Chen S., Furmaniak J., Smith B.R., Merino M.J., Nelson L.M. Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure. Fertil Steril. 2005; 84 (4): 958–65. doi: 10.1016/j.fertnstert.2005.04.060
  4. Welt C.K., Falorni A., Taylor A.E., Martin K.A., Hall J.E. Selective theca cell dysfunction in autoimmune oophoritis results in multifollicular development, decreased estradiol, and elevated inhibin B levels. J. Clin. Endocrinol Metab. 2005; 90 (5): 3069–76. doi: 10.1210/jc.2004-1985
  5. Welt C.K. Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin. Endocrinol. 2008; 68 (4): 499–509. doi: 10.1111/j.1365-2265.2007.03073.x
  6. Дмитриева М.Л., Тихоновская О.А., Логвинов С.В., Герасимов А.В., Потапов А.В., Варакута Е.Ю., Невоструев С.А. Динамика морфологических изменений репродуктивного аппарата яичника при экспериментальном аутоиммунном оофорите. Бюллетень сибирской медицины. 2012; 11 (1): 14–7. doi: 10.20538/1682-0363-2012-1-14-17. [Dmitrieva M.L., Tikhonovskaya O.A., Logvinov S.V., Gerasimov A.V., Potapov A.V., Varakuta E.Yu., Nevostruev S.A. Dynamics of morphological changes in ovarian reproductive apparatus in experimental autoimmune oophoritis. Bulletin of Siberian Medicine. 2012; 11 (1): 14–7. doi: 10.20538/1682-0363-2012-1-14-17 (In Russian)]
  7. Дмитриева М.Л., Тихоновская О.А., Невоструев С.А., Логвинов С.В., Муштоватова Л.С., Красноженов Е.П. Аутоиммунный компонент при воспалительных заболеваниях придатков матки. Врач-аспирант. 2012; 50 (1): 26–33. [Dmitrieva M.L., Tikhonovskaya O.A., Nevostruev S.A., Logvinov S.V., Mushtovatova L.S., Krasnozhenov E.P. Autoimmune component in inflammatory diseases of uterine appendages. Doctor-Postgraduate. 2012; 50 (1): 26–33 (In Russian)]
  8. Shapouri-Moghaddam A., Mohammadian S., Vazini H., Taghadosi M., Esmaeili S.A., Mardani F., Seifi B., Mohammadi A., Afshari J.T., Sahebkar A. Macrophage plasticity; polarization, and function in health and disease. J. Cell Physiol. 2018; 233 (9): 6425–40. doi: 10.1002/jcp.26429
  9. Lebovic D.I., Naz R. Premature ovarian failure: Think ‘autoimmune disorder’. Sexuality, Reproduction and Menopause. 2004; 2 (4): 230–3. doi: 10.1016/j.sram.2004.11.010
  10. Bats A.S., Barbarino P.M., Bene M.C., Faure G.C., Forges T. Local lymphocytic and epithelial activation in a case of autoimmune oophoritis. Fertil Steril. 2008; 90 (3): 849. doi: 10.1016/j.fertnstert.2007.08.048

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1.CD68+in the medulla of rat ovaries with autoimmune oophoritis model, immunohistochemical staining,×400: a) control group; b) day 15 of experiment

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3. Fig. 2.CD68+in the wall of growing follicle, immunohistochemical staining,×400: a) control group; b) day 10 of experiment

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4. Fig. 3.CD68+in the ovarian cortex on day 15 of experiment (main group), immunohistochemical staining,×400

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5. CD68+macrophage numerical density per 1 mm2(immunohistochemical staining), Me (Q1–Q3), cells/mm2

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