The Role of Oxidative Stress-Related Genes in Polycystic Ovary Syndrome: Insights into Genetic Susceptibility and Pathogenesis
- Authors: Ломтева С.В.1,2
-
Affiliations:
- CENTER OF HUMAN REPRODUCTION AND IVF
- Southern Federal University
- Section: Human ecological genetics
- Submitted: 15.05.2025
- Accepted: 01.10.2025
- Published: 01.10.2025
- URL: https://journals.eco-vector.com/ecolgenet/article/view/679724
- DOI: https://doi.org/10.17816/ecogen679724
- ID: 679724
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Abstract
Oxidative stress is a major factor in the development and progression of polycystic ovary syndrome (PCOS). It drives metabolic disturbances, systemic inflammation, and ovarian dysfunction. Excessive production of reactive oxygen species (ROS), combined with weakened antioxidant defenses, exacerbates insulin resistance, hyperandrogenism, and impaired folliculogenesis. Genetic variations in antioxidant genes further influence this imbalance, shaping individual susceptibility to PCOS.his review summarizes the role of key antioxidant defense genes, including SOD2, GPX1, GPX4, CAT, and PON1, and examines their associations with PCOS risk and clinical outcomes. Polymorphisms such as SOD2 rs4880 and GPX4 rs713041 show relatively consistent links with PCOS, whereas other variants display population-specific effects. Understanding the genetic basis of oxidative stress may advance biomarker discovery and support the development of personalized therapeutic strategies for women with PCOS.
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About the authors
Светлана Витальевна Ломтева
CENTER OF HUMAN REPRODUCTION AND IVF; Southern Federal University
Author for correspondence.
Email: embryolab61@gmail.com
ORCID iD: 0000-0002-8791-1936
Scopus Author ID: 6507751405
embryologist, Senior researcher, Ph.D. of Biological Sciences
Russian Federation
References
- Agarwal A, Gupta S, Sharma RK. Role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2005;3:28. doi: 10.1186/1477-7827-3-28.
- Li W, Liu C, Yang Q, et al. Oxidative stress and antioxidant imbalance in ovulation disorder in patients with polycystic ovary syndrome. Front Nutr. 2022;9:1018674. doi: 10.3389/fnut.2022.1018674.
- Ershova OA, Bairova TA, Kolesnikov SI, et al. Oxidative Stress and Catalase Gene. Bull. Exp. Biol. Med. 2016,161(3): 400–403. doi: 10.1007/S10517-016-3424-0.
- Phaniendra A, Jestadi DB, Periyasamy L. Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases. Indian J. Clin. Biochem. 2015;30(1):11–26. doi: 10.1007/s12291-014-0446-0.
- Bannigida DM, Nayak BS, Vijayaraghavan R. Insulin resistance and oxidative marker in women with PCOS. Arch. Physiol. Biochem. 2020,126(2): 183–86. doi: 10.1080/13813455.2018.1499120.
- Herman R, Jensterle M, Janež A, et al. Genetic Variability in Antioxidative and Inflammatory Pathways Modifies the Risk for PCOS and Influences Metabolic Profile of the Syndrome. Metabolites. 2020,10(11): 1–18. doi: 10.3390/METABO10110439.
- Murri M, Luque-ramírez M, Insenser M, et al. Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum. Reprod. Update. 2013,19(3): 268–88. doi: 10.1093/HUMUPD/DMS059.
- Terao H, Wada-Hiraike O, Nagumo A, et al. Role of oxidative stress in follicular fluid on embryos of patients undergoing assisted reproductive technology treatment. J. Obstet. Gynaecol. Res. 2019,45(9): 1884–91. doi: 10.1111/JOG.14040.
- Liu Y, Yu Z, Zhao S, et al. Oxidative stress markers in the follicular fluid of patients with polycystic ovary syndrome correlate with a decrease in embryo quality. J. Assist. Reprod. Genet. 2021,38(2): 471–77. doi: 10.1007/S10815-020-02014-Y.
- Bizoń A, Tchórz A, Madej P, et al. The Activity of Superoxide Dismutase, Its Relationship with the Concentration of Zinc and Copper and the Prevalence of rs2070424 Superoxide Dismutase Gene in Women with Polycystic Ovary Syndrome-Preliminary Study. J. Clin. Med. 2022,11(9). doi: 10.3390/JCM11092548.
- Singh AK, Chattopadhyay R, Chakravarty B, Chaudhury K. Markers of oxidative stress in follicular fluid of women with endometriosis and tubal infertility undergoing IVF. Reprod. Toxicol. 2013,42: 116–24. doi: 10.1016/J.REPROTOX.2013.08.005.
- Uçkan K, Demir H, Turan K, et al. Role of Oxidative Stress in Obese and Nonobese PCOS Patients. Int. J. Clin. Pract. 2022;2022:4579831. doi: 10.1155/2022/4579831.
- Rudnicka E, Duszewska AM, Kucharski M, et al. Оxidative stress and reproductive function: Oxidative stress in polycystic ovary syndrome. Reproduction. 2022,164(6): F145–54. doi: 10.1530/REP-22-0152.
- Duleba AJ, Dokras A. Is PCOS an inflammatory process? Fertil. Steril. 2012,97(1): 7–12. doi: 10.1016/J.FERTNSTERT.2011.11.023.
- Polat S, Şimşek Y. Five variants of the superoxide dismutase genes in Turkish women with polycystic ovary syndrome. Free Radic. Res. 2020,54(6): 467–76. doi: 10.1080/10715762.2020.1802022.
- Sun Y, Li S, Liu H, et al. Association of GPx1 P198L and CAT C-262T Genetic Variations With Polycystic Ovary Syndrome in Chinese Women. Front. Endocrinol. (Lausanne). 2019,10: 771. doi: 10.3389/FENDO.2019.00771.
- Yu N, Wu L, Xing X. NOX4 deficiency improves the impaired viability, inhibited the apoptosis and suppressed autophagy of DHEA-treated ovarian granulosa cells through inhibiting endoplasmic reticulum stress via inactivating PERK/ATF4 pathway. Tissue & Cell. 2025;92:102640. doi: 10.1016/j.tice.2024.102640.
- Wang Y, Li N, Zeng Z, et al. Humanin regulates oxidative stress in the ovaries of polycystic ovary syndrome patients via the Keap1/Nrf2 pathway. Mol. Hum. Reprod. 2021,27(2). doi: 10.1093/MOLEHR/GAAA081.
- Duică F, Dănilă CA, Boboc AE, et al. Impact of Increased Oxidative Stress on Cardiovascular Diseases in Women With Polycystic Ovary Syndrome. Front Endocrinol (Lausanne). 2021;12:614679. doi: 10.3389/fendo.2021.614679.
- Sulaiman MAH, Al-Farsi YM, Al-Khaduri MM, et al. Polycystic ovarian syndrome is linked to increased oxidative stress in Omani women. Int. J. Womens. Health. 2018,10: 763. doi: 10.2147/IJWH.S166461.
- Nawar AS, Alwan ZHO, Sheikh QI. Gene expression and plasma level of CuZn and Mn superoxide dismutase in Iraqi women with polycystic ovary syndrome. Med. J. Babylon. 2022,19(4): 691–96. doi: 10.4103/MJBL.MJBL_221_22.
- Talat A, Satyanarayana P, Anand P. Association of Superoxide Dismutase Level in Women with Polycystic Ovary Syndrome. J. Obstet. Gynecol. India. 2022,72(1): 6–12. doi: 10.1007/S13224-021-01430-z.
- Agarwal A, Tadros H, Tvrdá E. Role of oxidants and antioxidants in female reproduction. In: Armstrong D, Stratton RD (eds.) Oxidative Stress and Antioxidant Protection: The Science of Free Radical Biology and Disease. Hoboken, NJ: Wiley Blackwell; 2016:253–280. doi: 10.1002/9781118832431.ch16.
- González F, Minium J, Rote NS, Kirwan JP. Hyperglycemia alters tumor necrosis factor-alpha release from mononuclear cells in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 2005,90(9): 5336–42. doi: 10.1210/JC.2005-0694.
- Yilmaz Ö, Calan M, Kume T, et al. The effect of prolactin levels on MPV in women with PCOS. Clin. Endocrinol. (Oxf). 2015,82(5): 747–52. doi: 10.1111/CEN.12647.
- Zhang J, Bao Y, Zhou X, Zheng L. Polycystic ovary syndrome and mitochondrial dysfunction. Reprod Biol Endocrinol. 2019;17:67. doi: 10.1186/s12958-019-0509-4.
- Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999,6(2): 99–104. doi: 10.1038/SJ.CDD.4400476.
- Uyanikoglu H, Sabuncu T, Dursun H, et al. Circulating levels of apoptotic markers and oxidative stress parameters in women with polycystic ovary syndrome: a case-controlled descriptive study. Biomarkers. 2017,22(7): 643–47. doi: 10.1080/1354750X.2016.1265004.
- Nakagawa K, Hisano M, Sugiyama R, Yamaguchi K. Measurement of oxidative stress in the follicular fluid of infertility patients with an endometrioma. Arch. Gynecol. Obstet. 2016,293(1): 197–202. doi: 10.1007/S00404-015-3834-7.
- Jozwik M, Wolczynski S, Jozwik M, Szamatowicz M. Oxidative stress markers in preovulatory follicular fluid in humans. Mol. Hum. Reprod. 1999,5(5): 409–13. doi: 10.1093/MOLEHR/5.5.409.
- Prabhu YD, Borthakur A, A.G S, et al. Increased pro-inflammatory cytokines in ovary and effect of γ-linolenic acid on adipose tissue inflammation in a polycystic ovary syndrome model. J. Reprod. Immunol. 2021,146. doi: 10.1016/J.JRI.2021.103345.
- Li Y, Zhang J, Liu Y-D, et al. Long non-coding RNA TUG1 and its molecular mechanisms in polycystic ovary syndrome. RNA Biol. 2020,17(12): 1798–1810. doi: 10.1080/15476286.2020.1783850.
- Victor VM, Rovira-Llopis S, Bañuls C, et al. Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase. PLoS One. 2016,11(3). doi: 10.1371/JOURNAL.PONE.0151960.
- Dabravolski SA, Nikiforov NG, Eid AH, et al. Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome. Int. J. Mol. Sci. 2021,22(8). doi: 10.3390/IJMS22083923.
- Lomteva, S. V., Shkurat, T. P., Bugrimova, E. S., Zolotykh, O. S., Alexandrova, A. A., & Karantysh, G. V. (2022). Violation of the Hormonal Spectrum in Polycystic Ovaries in Combination with Insulin Resistance. What is the Trigger: Insulin Resistance or Polycystic Ovary Disease?. Baghdad Science Journal, 19(5), 20.
- Sugino N, Takiguchi S, Kashida S, et al. Superoxide dismutase expression in the human corpus luteum during the menstrual cycle and in early pregnancy. Mol. Hum. Reprod. 2000,6(1): 19–25. doi: 10.1093/MOLEHR/6.1.19.
- Rice S, Christoforidis N, Gadd C, et al. Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries. Hum. Reprod. 2005,20(2): 373–81. doi: 10.1093/HUMREP/DEH609.
- Zhao H, Zhang J, Cheng X, et al. Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment. J. Ovarian Res. 2023,16(1). doi: 10.1186/S13048-022-01091-0.
- Dupont J, Scaramuzzi RJ. Insulin signalling and glucose transport in the ovary and ovarian function during the ovarian cycle. Biochem. J. 2016,473(11): 1483–1501. doi: 10.1042/BCJ20160124.
- Zuo T, Zhu M, Xu W. Roles of Oxidative Stress in Polycystic Ovary Syndrome and Cancers. Oxid. Med. Cell. Longev. 2016,14. doi: 10.1155/2016/8589318.
- Shkurat, M. A., Mashkina, E. V., Milyutina, N. P., & Shkurat, T. P. (2023). The role of polymorphism of redox-sensitive genes in the mechanisms of oxidative stress in obesity and metabolic diseases. Ecological genetics, 21(3), 261-287.
- Shkurat M.A., Mashkina E.V., Milyutina N.P., Shkurat T.P.Polymorphism of Antioxidant Genes and Overweight in Children // Russian Journal of Genetics. - 2024. - Т. 60. - №7. - С. 954. doi: 10.1134/S102279542470039X
- Ali, R. M., Lomteva, S. V., Aleksandrova, A. A., Ammar,M. N. A., Bulanov, I. G., & Shkurat, T . P. (2025). Association of the superoxide dismutase 2 (SOD2) gene polymorphic locus rs4880 with polycystic ovary syndrome: a meta-analysis. Scientific Advances in Biomedical Research, 11(1), 57-74.
- Ali RM, Lomteva SV, Aleksandrova AA, et al. Effect of polymorphisms CYP17 (rs743572), SOD2 (rs4880) and CAT (rs1001179) on hormonal profile and redox status of blood serum and follicular fluid in patients with polycystic ovary syndrome. Gene Reports. 2023,33: 101817. doi: 10.1016/J.GENREP.2023.101817.
- Alkhuriji AF, Alomar SY, Babay ZA, et al. Association SOD2 and PON1 Gene Polymorphisms with Polycystic Ovary Syndrome in Saudi Women. Mol. Syndromol. 2021,13(2): 117–22. doi: 10.1159/000519527.
- Liu Q, Liu H, Bai H, et al. Association of SOD2 A16V and PON2 S311C polymorphisms with polycystic ovary syndrome in Chinese women. J. Endocrinol. Invest. 2019,42(8): 909–21. doi: 10.1007/S40618-018-0999-5.
- Arslan AO, Celik F, Kucukhuseyin O, et al. Investigation of variants of critically important antioxidant enzyme genes in patients with polycystic ovary syndrome. Exp. Biomed. Res. 2019,2(1): 8–19. doi: 10.30714/J-EBR.2019147578.
- Salahshoor MR, Sohrabi M, Jalili F, et al. No evidence for a major effect of three common polymorphisms of the GPx1, MnSOD, and CAT genes on PCOS susceptibility. J. Cell. Biochem. 2018,1
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