Sribna V. O., Lytvynenko A. P., Kaleynikova O. M., Voznesenska T. Yu., Blashkiv T. V.

EXPERIMENTAL MODEL OF PREMATURE OVARIAN INSUFFICIENCY: COMORBIDITY OF DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE

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Sribna V. O., Lytvynenko A. P., Kaleynikova O. M., Voznesenska T. Yu., Blashkiv T. V.

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CLINICAL AND EXPERIMENTAL MEDICINE

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Scientific article

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Premature ovarian failure (POF) is a pathological condition characterized by decreased ovarian reserve and impaired folliculogenesis in women under 40 years of age. Modern experimental models of POF, in particular those induced by cyclophosphamide, busulfan, or D-galactose, primarily reflect local toxic damage to the gonads and do not account for systemic metabolic changes inherent to chronic diseases. The aim of the work was to study the parameters of meiotic maturation and morphological quality of oocytes, as well as the pathways of cell death in their follicular environment under the comorbid effects of diabetes mellitus (DM) and chronic kidney disease (CKD) to create a comprehensive, biologically relevant experimental model of POF. The studies were conducted using sexually mature white laboratory mice divided into three groups: control, DM, and DM+CKD. The diabetes model was reproduced by the administration of streptozotocin and nicotinamide, CKD - by repeated immunization with renal antigen. The viability of cells in the follicular environment of oocytes was assessed by the method of in vivo double staining with fluorescent dyes, and the meiotic maturation of oocytes and their quality – by morphological criteria. The results obtained indicate that the combined pathology of DM and CKD leads to a pronounced impairment of ovarian function, an increase in the proportion of cells with signs of apoptosis and necrosis, a decrease in the morphological quality of oocytes and a violation of meiotic maturation of oocytes at the stage of metaphase I and II. The developed POF model adequately reflects the influence of metabolic and systemic changes and can be effectively used for fur- ther study of the mechanisms of ovarian damage and testing new approaches to preserving reproductive function.

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Bibliography:

1. Li M, Zhu Y, Wei J, Chen L, Chen S, Lai D. The global prevalence of premature ovarian insufficiency: a systematic review and meta- analysis. Climacteric. 2023;26(2):95-102. DOI: 10.1080/13697137.2022.2153033.
2. Panay N, Anderson RA, Bennie A, Cedars M, Davies M, Ee C, et al.; ESHRE, ASRM, CREWHIRL, and IMS Guideline Group on POI. Evidence-based guideline: premature ovarian insufficiency. Hum Reprod Open. 2024;2024(4):hoae065. DOI: 10.1093/hropen/hoae065.
3. Jones AR, Enticott J, Ebeling PR, Mishra GD, Teede HT, Vincent AJ. Bone health in women with premature ovarian insufficiency/early menopause: a 23-year longitudinal analysis. Hum Reprod. 2024;39(5):1013-1022. DOI: 10.1093/humrep/deae037.
4. Karamitrou EK, Anagnostis P, Vaitsi K, Athanasiadis L, Goulis DG. Early menopause and premature ovarian insufficiency are associated with increased risk of dementia: a systematic review and meta-analysis of observational studies. Maturitas. 2023;176:107792. DOI: 10.1016/j.maturitas.2023.107792.
5. Jha JC, Banal C, Chow BS, Cooper ME, Jandeleit-Dahm K. Diabetes and kidney disease: role of oxidative stress. Antioxid Redox Signal. 2016;25(12):657-684. DOI: 10.1089/ars.2016.6664.
6. Tucker PS, Scanlan AT, Dalbo VJ. Chronic kidney disease influences multiple systems: describing the relationship between oxidative stress, inflammation, kidney damage, and concomitant disease. Oxid Med Cell Longev. 2015;2015:806358. DOI: 10.1155/2015/806358.
7. Tang D, Feng X, Ling L, Zhang W, Luo Y, Wang Y, et al. Experimental study for the establishment of a chemotherapy-induced ovarian insufficiency model in rats by using cyclophosphamide combined with busulfan. Regul Toxicol Pharmacol. 2021;122:104915. DOI: 10.1016/j.yrtph.2021.104915.
8. Cao LB, Leung CK, Law PW, Lv Y, Ng CH, Liu HB, et al. Systemic changes in a mouse model of VCD-induced premature ovarian failure. Life Sci. 2020;262:118543. DOI: 10.1016/j.lfs.2020.118543.
9. Dai F, Wang R, Deng Z, Yang D, Wang L, Wu M, et al. Comparison of the different animal modeling and therapy methods of premature ovarian failure in animal model. Stem Cell Res Ther. 2023;14:135. DOI: 10.1186/s13287-023-03333-4.
10. Ahangarpour A, Oroojan AA, Khorsandi L, Arzani G, Afshari G. Effects of betulinic acid on the male reproductive system of a streptozotocin- nicotinamide-induced diabetic mouse model. World J Mens Health. 2016;34(3):209-216. DOI: 10.5534/wjmh.2016.34.3.209.
11. Stupchuk MS, Voznesenska TY, Hrushka N, Shepel OD, Dzhuran BV, Blashkiv TV, vynakhidnyky; Instytut fiziolohiyi im. O.O. Bohomoltsya NANU, patentovlasnyk. Sposib modelyuvannya systemnoho autoimunnoho ushkodzhennya u myshey. Patent Ukrainy № 120418. 2017 Zhovt 25. [in Ukrainian].
12. Shimizu S, Eguchi Y, Kamiike W, Akao Y, Kosaka H, Hasegawa J, et al. Involvement of ICE family proteases in apoptosis induced by reoxygenation of hypoxic hepatocytes. Am J Physiol Gastrointest Liver Physiol. 1996;271(6 Pt 1):G949-G958. DOI: 10.1152/ajpgi.1996.271.6.G949.
13. Liang J, Gao Y, Feng Z, Zhang B, Na Z. Reactive oxygen species and ovarian diseases: antioxidant strategies. Redox Biol. 2023;62:102659. DOI: 10.1016/j.redox.2023.102659.
14. Yan H, Wang L, Zhang G, Li N, Zhao Y, Liu J, et al. Oxidative stress and energy metabolism abnormalities in polycystic ovary syndrome: from mechanisms to therapeutic strategies. Reprod Biol Endocrinol. 2024;22:159. DOI: 10.1186/s12958-024-01337-0.
15. Xue H, Hu Z, Liu S, Zhang S, Yang W, Li J, et al. The mechanism of NF-κB-TERT feedback regulation of granulosa cell apoptosis in PCOS rats. PLoS One. 2024;19(10):e0312115. DOI: 10.1371/journal.pone.0312115.
16. Qin X, Du J, He R, Li Y, Zhu Q, Li Y, et al. Adverse effects of type 2 diabetes mellitus on ovarian reserve and pregnancy outcomes during the assisted reproductive technology process. Front Endocrinol (Lausanne). 2023;14:1274327. DOI: 10.3389/fendo.2023.1274327.
17. Wang Y, Wang Y. Accelerated ovarian aging among type 2 diabetes patients and its association with adverse lipid profile. Front Endocrinol (Lausanne). 2022;13:780979. DOI: 10.3389/fendo.2022.780979.
18. Helal J, Fatema K, Hasan MJ. Reproductive dysfunction in chronic kidney disease: a focus on male and female infertility. J Kidney Dis Reprod. 2025;7(1):1-10. DOI: 10.22259/2639-3573.0701001.

Publication of the article:

«Bulletin of problems biology and medicine», 2025 Issue 4, 179, 194-201 pages, index UDC 616-092.9:618.173-06:616.379-008.64+616.61-002.2

DOI:

10.29254/2077-4214-2025-4-179-194-201