Research Article

Effects of antioxidants used in the experimental premature ovarian insufficiency model on mitophagy proteins and them-associated MicroRNAs

Volume: 64 Number: 4 December 8, 2025
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Effects of antioxidants used in the experimental premature ovarian insufficiency model on mitophagy proteins and them-associated MicroRNAs

Abstract

Aim: It was aimed to investigate the protective and therapeutic effects of quercetin and curcumin in POI by examining follicle count, immunohistochemical proteins, mRNAs and their related microRNAs. Materials and Methods: In our study, an experimental premature ovarian insufficiency model was created on rats by means of cyclophosphamide. Then the tissues were examined by histopathological methods and histochemical staining. We studied the changes in parkin-dependent and independent mechanisms that occur with quercetin and curcumin. RNA isolation was performed on ovarian samples and cDNA synthesis, and qPCR processes were performed. The difference between the obtained findings and the groups was evaluated statistically. Results: Cyclophosphamide depleted primordial follicles, which is the main pool for fertility, on ovarian tissue and induced atresia (p<0.001). Curcumin and quercetin acted on parkin-dependent pathways, resulting in significant improvement in the ovarian follicle pool (p<0.001). Conclusion: The significant increase in the primordial follicle pool and the decrease in the rate of atretic follicles observed in the groups given curcumin and quercetin indicate that curcumin and quercetin have protective and therapeutic roles in the pathogenesis of POI by regulating mitophagy in the parkin-mediated pathway on the ovary.

Keywords

References

  1. Armeni E, Paschou SA, Goulis DG, Lambrinoudaki I. Hormone therapy regimens for managing the menopause and premature ovarian insufficiency. Best Pract Res Clin Endocrinol Metab. 2021;35: 101561. 10.1016/j.beem.2021.101561.
  2. Mo J, Hu H, Li P, Ye Y, Chen W, Chen L, Qiao J, Zhao X, Yan Q, Chen C. Human hair follicle-derived mesenchymal stem cells improve ovarian function in cyclophosphamide-induced POF mice. Stem Cell Res Ther. 2025 Feb 11;16(1):67. doi: 10.1186/s13287-024-04097-1. PMID: 39934888; PMCID: PMC11816600.
  3. Yu Z, Peng W, Li F, Fu X, Wang J, Ding H, et al. Integrated metabolomics and transcriptomics to reveal biomarkers and mitochondrial metabolic dysregulation of premature ovarian insufficiency. Front Endocrinol. 2023;14: 1280248. 10.3389/fendo.2023.1280248.
  4. Feng S, Wan S, Liu S, Wang W, Tang M, Bai L, et al. LARS2 regulates apoptosis via ROS-mediated mitochondrial dysfunction and endoplasmic reticulum stress in ovarian granulosa cells. Oxid Med Cell Longev. 2022;2022: 5501346. 10.1155/2022/5501346.
  5. Zhao Y, Zhang Y, Liu D, Feng H, Wang X, Su J, Yao Y, Ng EHY, Yeung WSB, Li RHW, Rodriguez-Wallberg KA, Liu K. Identification of curcumin as a novel potential drug for promoting the development of small ovarian follicles for infertility treatment. PNAS Nexus. 2022 Jul 8;1(3):pgac108. doi: 10.1093/pnasnexus/pgac108. Erratum in: PNAS Nexus. 2023 Feb 15;2(2):pgad010. doi: 10.1093/pnasnexus/pgad010. PMID: 36741430; PMCID: PMC9896916.
  6. Lv Y, Cao RC, Liu HB, Su XW, Lu G, Ma JL, Chan WY. Single-Oocyte Gene Expression Suggests That Curcumin Can Protect the Ovarian Reserve by Regulating the PTEN-AKT-FOXO3a Pathway. Int J Mol Sci. 2021 Jun 18;22(12):6570. doi: 10.3390/ijms22126570. PMID: 34207376; PMCID: PMC8235657.
  7. Ji M, Weng S, Li X, Xiao Q, Tong Y, Zhou Y, Luo T, Liu Z. Revitalizing premature ovarian failure: quercetin counteracts imatinib-induced apoptosis via the PI3K/AKT signaling pathway based on network pharmacology. Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan;398(1):833-842. doi: 10.1007/s00210-024-03293-3. Epub 2024 Jul 29. PMID: 39073414.
  8. Luo J, Sun Z. MicroRNAs in POI, DOR and POR. Arch Gynecol Obstet. 2023 Nov;308(5):1419-1430. doi: 10.1007/s00404-023-06922-z. Epub 2023 Feb 25. PMID: 36840768.

Details

Primary Language

English

Subjects

Obstetrics and Gynaecology

Journal Section

Research Article

Publication Date

December 8, 2025

Submission Date

May 22, 2025

Acceptance Date

August 28, 2025

Published in Issue

Year 2025 Volume: 64 Number: 4

Vancouver
1.Duygu Uçar Kartal, Naci Kemal Kuşçu, Kemal Özbilgin, Muhammed Yusuf Pekmezci. Effects of antioxidants used in the experimental premature ovarian insufficiency model on mitophagy proteins and them-associated MicroRNAs. EJM. 2025 Dec. 1;64(4):688-700. doi:10.19161/etd.1704479

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