Study of inflammatory and angiogenic biomarker levels in various biological fluids in women with extragenital endometriosis
Kudryavtseva E.V., Mangileva Ya.A., Polushina L.G., Maksimova A.Yu., Kopenkin M.A., Zornikov D.L., Kovalev V.V.
Objective: To analyze the content of biomarkers of inflammation and angiogenesis in oral and peritoneal fluids in women with a common form of extragenital endometriosis including ovarian lesions.
Materials and methods: This was a comparative observational study. Group 1 (n=88) consisted of women with confirmed extragenital endometriosis including endometrioid ovarian cysts; group 2 (n=30) consisted of healthy women without signs of endometriosis. The samples of oral fluid (OF) were collected from all participants of the study, and samples of peritoneal fluid (PF) were collected from women of group 1. The levels of vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), and interleukins (IL), namely IL-1β, IL-6, IL-8, and IL-10 were studied in biological fluids.
Results: The level of VEGF in OF was significantly higher in the patients of group 1, namely 906.4 (281.9–178) pg/ml compared to the patients of group 2, 241.9 (105.225–324.475) pg/ml, p<0.001. The level of IL-8 was also significantly higher in group 1 compared to group 2, 100.85 (23.333–208.7) pg/ml versus 11.34 (6.549–21.205) pg/ml, respectively, p<0.001. The levels of TNF-α, IL-6, and IL-10 were higher in group 2. The analysis of the correlation between the levels of markers in OF and PF showed no correlation for IL-8, IL-10 and TNF-α and the presence of a very weak, nonlinear relationship for IL-1β, IL-6 and VEGF.
Conclusion: The data obtained suggest the independence of inflammatory and angiogenic biomarker profiles in different biological compartments. The results highlight the potential for future research into OF as a potential bio substrate that could indirectly reflect the characteristics of the systemic inflammatory response in patients with extragenital endometriosis.
Authors’ contributions: Kudryavtseva E.V., Kovalev V.V. – developing the concept and design of the study; Mangileva Ya.A., Polushina L.G., Kopenkin M.A., Maksimova A.Yu. – collecting and processing the material; Kudryavtseva E.V., Zornikov D.L. – statistical processing of the data; Kudryavtseva E.V., Mangileva Ya.A. – writing the text; Zornikov D.L., Kovalev V.V. – editing the article.
Conflicts of interest: The authors declare no possible conflicts of interest.
Funding: The study was conducted without sponsorship.
Ethical Approval: The study was approved by the Ethical Review Board of the Ural State Medical University, Ministry of Health of Russia (Protocol No.11 dated 24/12/2021).
Patient Consent for Publication: The patients signed informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Kudryavtseva E.V., Mangileva Ya.A., Polushina L.G., Maksimova A.Yu., Kopenkin M.A.,
Zornikov D.L., Kovalev V.V. Study of inflammatory and angiogenic biomarker levels in various
biological fluids in women with extragenital endometriosis.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (7): 112-120 (in Russian)
https://dx.doi.org/10.18565/aig.2025.116
Keywords
References
- Horne A.W., Missmer S.A. Pathophysiology, diagnosis, and management of endometriosis. BMJ. 2022: e070750. https://dx.doi.org/10.1136/bmj-2022-070750
- Адамян Л.В., Андреева Е.Н. Эндометриоз и его глобальное влияние на организм женщины. Проблемы репродукции. 2022; 28: 54-64. [Adamyan L.V., Andreeva E.N. Endometriosis and its global impact on a woman’s body. Russian Journal of Human Reproduction. 2022; 28(1): 54 64 (in Russian)]. https://dx.doi.org/10.17116/repro20222801154
- Shimura K., Tarumi Y., Fujii M., Ogawa K., Maeda E., Tanaka Y. et al. Low-nutrient environment-induced changes in inflammation, cell proliferation, and PGC-1α expression in stromal cells with ovarian endometriosis. Reprod. Sci. 2022; 30: 1094-102. https://dx.doi.org/10.1007/s43032-022-01089-5
- Didziokaitė G., Biliute G., Gudaite J., Kvedarienė V. Oxidative stress as a potential underlying cause of minimal and mild endometriosis-related infertility. Int. J. Mol. Sci. 2023; 24(4): 3809. https://dx.doi.org/10.3390/ijms24043809
- Дубровина С.О., Берлим Ю.Д., Александрина А.Д., Вовкочина М.А., Богунова Д.Ю., Гимбут В.С., Божинская Д.М. Современные представления о диагностике и лечении эндометриоза. Акушерство и гинекология. 2023: 2: 146-53. [Dubrovina S.O., Berlim Yu.D., Aleksandrina A.D., Vovkochina M.A., Bogunova D.Yu., Gimbut V.S., Bozhinskaya D.M. Modern ideas about the diagnosis and treatment of endometriosis. Obstetrics and Gynecology. 2023; (2): 146-53 (in Russian)]. https://dx.doi.org/10.18565/aig.2023.43
- Li W., LibinWeng. Examination on risk factors of infertility caused by EMT and their correlation with VEGF, TNF-α, IL-6, IL-10, and IL-17. Contrast Media Mol. Imaging. 2022; 2022: 4421418. https://dx.doi.org/10.1155/2022/4421418
- Nanda A., Thangapandi K., Banerjee P., Dutta M., Wangdi T., Sharma P. et al. Cytokines, angiogenesis, and extracellular matrix degradation are augmented by oxidative stress in endometriosis. Ann. Lab. Med. 2020; 40(5): 390-7. https://dx.doi.org/10.3343/alm.2020.40.5.390
- Liu Y., Fu H., Zuo L. Anti-inflammatory activities of a new VEGF blocker, conbercept. Immunopharmacol. Immunotoxicol. 2021; 43(5): 594-8. https://dx.doi.org/10.1080/08923973.2021.1959608
- Akhmedova S.R., Omarov N.S.M. Determination of cytokine status indicators and angiogenesis factors in patients with external genital endometriosis and vitamin D deficiency. Periodico Tche Quimica. 2020; 17(34): 251-9. https://dx.doi.org/10.52571/PTQ.v17.n34.2020.268_P34_pgs_251_259.pdf
- Кудрявцева Е.В., Геец А.В., Мангилева Я.А., Чижова А.В., Пацюк О.В. Современные неинвазивные методы диагностики эндометриоза. Уральский медицинский журнал. 2023; 22(4): 140-7. [Kudryavtseva E.V., Geets A.V., Mangileva Y.A., Chizhova A.V., Patsyuk O.V. Modern non-invasive diagnosis of endometriosis. Ural Medical Journal. 2023; 22(4): 140-7 (in Russian)]. https://dx.doi.org/10.52420/2071-5943-2023-22-4-140-147
- Ferrier C., Bendifallah S., Suisse S., Dabi Y., Touboul C., Puchar A. et al. Saliva microRNA signature to diagnose endometriosis: a cost‐effectiveness evaluation of the Endotest®. BJOG 2022; 130(4): 396-406. https://dx.doi.org/10.1111/1471-0528.17348
- Dabi Y., Suisse S., Puchar A., Delbos L., Poilblanc M., Descamps P. et al. Endometriosis-associated infertility diagnosis based on saliva microRNA signatures. Reprod. Biomed. Online. 2023; 46(1): 138-49. https://dx.doi.org/10.1016/j.rbmo.2022.09.019
- Борисова А.В., Чаговец В.В., Козаченко А.В., Стародубцева Н.Л., Кононихин А.С., Салимова Д.Ф., Коган Е.А., Адамян Л.В., Франкевич В.Е., Сухих Г.Т. Сравнительный анализ липидного состава перитонеальной жидкости и плазмы крови у пациенток с наружным генитальным эндометриозом и миомой матки. Акушерство и гинекология. 2017; 6: 74-82. [Borisova A.V., Chagovets V.V., Kozachenko A.V., Starodubtseva N.L., Kononikhin A.S., Salimova D.F., Kogan E.A., Adamyan L.V., Frankevich V.E., Sukhikh G.T. Comparative analysis of the lipid composition of peritoneal fluid and blood plasma in patients with external genital endometriosis and uterine myoma. Obstetrics and Gynecology. 2017; (6): 74-82 (in Russian)]. https://dx.doi.org/10.18565/aig.2017.6.74-82
- Копенкин М.А., Басова Е.А., Полушина Л.Г., Базарный В.В. Стабильность аналитов ротовой жидкости при разных условиях центрифугирования. Вестник УГМУ. 2024; 2: 7-18. [Kopenkin M.A., Basova E.A., Polushina L.G., Bazarny V.V. Stability of oral fluid analytes under different centrifugation conditions. USMU Medical Bulletin. 2024; 2: 7-18 (in Russian)].
- Bakun O. A modern noninvasive methods of diagnosis genital endometriosis associated with infertility. Clinical Anatomy and Operative Surgery. 2024; 23(1): 153-9. https://dx.doi.org/10.24061/1727-0847.23.1.2024.21
- Perricos A., Proestling K., Husslein H., Kuessel L., Hudson Q.J., Wenzl R. et al. Hsa-mir-135a shows potential as a putative diagnostic biomarker in saliva and plasma for endometriosis. Biomolecules. 2022; 12(8): 1144. https://dx.doi.org/10.3390/biom12081144
- Brulport A., Bourdon M., Vaiman D., Drouet C., Pocate-Cheriet K., Bouzid K. et al. An integrated multi-tissue approach for endometriosis candidate biomarkers: a systematic review. Reprod. Biol. Endocrinol. 2024; 22(1): 21. https://dx.doi.org/10.1186/s12958-023-01181-8
- Rahmioglu N., Fassbender A., Vitonis A.F., Tworoger S.S., Hummelshoj L., D’Hooghe T.M. et al. World endometriosis research foundation endometriosis phenome and Biobanking harmonization project: III. Fluid biospecimen collection, processing, and storage in endometriosis research. Fertil. Steril. 2014; 102(5): 1233-43. https://dx.doi.org/10.1016/j.fertnstert.2014.07.1208
- Lamceva J., Uljanovs R., Strumfa I. The main theories on the pathogenesis of endometriosis. Int. J. Mol. Sci. 2023; 24(5): 4254. https://dx.doi.org/10.3390/ijms24054254
- Zhang P., Wang G. Progesterone resistance in endometriosis: current evidence and putative mechanisms. Int. J. Mol. Sci. 2023; 24(8): 6992. https://dx.doi.org/10.3390/ijms24086992
- Kovalak E.E., Karacan T., Zengi O., Akgül Ö.K., Özyürek Ş.E., Güraslan H. Evaluation of new biomarkers in stage III and IV endometriosis. Gynecol. Endocrinol. 2023; 39(1): 2217290. https://dx.doi.org/10.1080/09513590.2023.2217290
- Chen S., Liu Y., Zhong Z., Wei C., Liu Y., Zhu X. Peritoneal immune microenvironment of endometriosis: role and therapeutic perspectives. Front. Immunol. 2023; 14: 1134663. https://dx.doi.org/10.3389/fimmu.2023.1134663
- Sun S., Zhang H., Zhong P., Xu Z. The effect of letrozole combined with dydrogesterone for endometriosis in China: a meta-analysis. Biomed. Res. Int. 2021; 9946060. https://dx.doi.org/10.1155/2021/9946060
- Aliabad R.A., Hassanpour K., Norooznezhad A.H. Cannabidiol as a possible treatment for endometriosis through suppression of inflammation and angiogenesis. Immun. Inflamm. Dis. 2024; 12(8): e1370. https://dx.doi.org/10.1002/iid3.1370
- Nishimoto-Kakiuchi A., Sato I., Nakano K., Ohmori H., Kayukawa Y., Tanimura H. et al. A long-acting anti-IL-8 antibody improves inflammation and fibrosis in endometriosis. Sci. Transl. Med. 2023; 15(684): eabq5858. https://dx.doi.org/10.1126/scitranslmed.abq5858
- Singh A.K., Dutta M., Chattopadhyay R., Chakravarty B., Chaudhury K. Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis. J. Assist. Reprod. Genet. 2016; 33: 1363-72. https://doi.org/10.1007/s10815-016-0782-5
- Scheck S.M., Henry C., Bedford N., Abbott J., Wynn‐Williams M., Yazdani A. et al. Non‐invasive tests for endometriosis are here; how reliable are they, and what should we do with the results? Austr. N. Z. J. Obstet. Gynaecol. 2024; 64(2):168-70. https://dx.doi.org/10.1111/ajo.13765
- Chou L.C., Fu C.Y. An empirical analysis of land property lawsuits and rainfalls. Springerplus. 2016; 5: 1. https://dx.doi.org/10.1186/s40064-015-1659-2
- Akoglu H. User’s guide to correlation coefficients. Turk. J. Emerg. Med. 2018; 18(3): 91-3. https://dx.doi.org/10.1016/j.tjem.2018.08.001
Received 30.04.2025
Accepted 18.06.2025
About the Authors
Elena V. Kudryavtseva, Dr. Med. Sci., Associate Professor, Professor at the Department of Obstetrics and Gynecology, A.B. Blokhin Ural Institute of Healthcare Management, 620075, Russia, Yekaterinburg, K. Liebknecht str., 8-B, elenavladpopova@yandex.ru, https://orcid.org/0000-0003-2797-1926Yana A. Mangileva, Obstetrician-Gynecologist, UGMK-Health LLC, 620144, Russia, Yekaterinburg, Sheinkman str., 113, bld. 2, yanaamangileva@mail.ru,
https://orcid.org/0000-0001-5693-0264
Larisa G. Polushina, PhD, Senior Researcher at the Central Research Laboratory, Ural State Medical University, Ministry of Health of Russia, 620024, Russia, Yekaterinburg, Repin str., 3, polushina-larisa@bk.ru, https://orcid.org/0000-0002-4921-7222
Arina Yu. Maksimova, PhD, Researcher at the Central Research Laboratory, Ural State Medical University, Ministry of Health of Russia, 620024, Russia, Yekaterinburg,
Repin str., 3, oreshek92@list.ru, https://orcid.org/0000-0001-8412-4315
Maxim A. Kopenkin, Junior Researcher at the Central Research Laboratory, Ural State Medical University, Ministry of Health of Russia, 620024, Russia, Yekaterinburg,
Repin str., 3, maximkopenkin@yandex.ru, https://orcid.org/0000-0002-6092-3734
Danila L. Zornikov, PhD, Associate Professor, Department of Medical Microbiology and Clinical Laboratory Diagnostics, Ural State Medical University, Ministry of Health
of Russia, 620024, Russia, Yekaterinburg, Repin str., 3, zornikovdl@yandex.ru, https://orcid.org/0000-0001-9132-215X
Vladislav V. Kovalev, Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology, A.B. Blokhin Ural Institute of Healthcare Management,
620075, Russia, Yekaterinburg, K. Liebknecht str., 8-B, vvkovalev55@gmail.com, https://orcid.org/0000-0001-8640-8418
Corresponding author: Elena V. Kudryavtseva, elenavladpopova@yandex.ru