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

Duygu Uçar Kartal; Naci Kemal Kuşçu; Kemal Özbilgin; Muhammed Yusuf Pekmezci

doi:10.19161/etd.1704479

Research Article

Deneysel prematüre yumurtalık yetmezliği modelinde kullanılan antioksidanların mitofaji proteinleri ve bunlarla ilişkili MikroRNA'lar üzerindeki etkileri

Year 2025, Volume: 64 Issue: 4, 688 - 700, 08.12.2025

Duygu Uçar Kartal , Naci Kemal Kuşçu , Kemal Özbilgin , Muhammed Yusuf Pekmezci

https://doi.org/10.19161/etd.1704479

Abstract

Amaç: Deneysel olarak Prematür Ovaryen Yetmezlik (POI) oluşturulmuş sıçanlar üzerinde; quercetin ve curcumin ile parkin bağımlı ve bağımsız mekanizmalarda meydana gelen değişiklikler inceledi. Folikül sayısı, immünohistokimyasal proteinler, mRNA'lar ve bunlarla ilişkili mikroRNA'ları inceleyerek POI'de quercetin ve curcuminin koruyucu ve tedavi edici etkilerini araştırmak amaçlandı.
Gereç ve Yöntem: Çalışmamızda sıçanlarda siklofosfamid aracılığıyla deneysel prematüre over yetmezliği modeli oluşturuldu. Daha sonra dokular histopatolojik yöntemler ve histokimyasal boyama ile incelendi. Over örneklerinde RNA izolasyonu yapıldı ve cDNA sentezi ve qPCR işlemleri gerçekleştirildi.
Bulgular: Elde edilen bulgular ile gruplar arasındaki fark istatistiksel olarak değerlendirildi.

Keywords

Siklofosfamid , Kurkumin , Kuersetin , MiRNA , POI , Parkin , FUNDC1.

References

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.
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.
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.
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.
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.
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.
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.
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.
Chon SJ, Umair Z, Yoon M-S. Premature Ovarian Insufficiency: Past, Present, and Future. Front Cell Dev Biol 2021;9. https://doi.org/10.3389/fcell.2021.672890.
Jiang B, Hong N, Zhang L, Xu B, He Q, Qian X, Li F, Dong F. MiR-181a-5p may regulate cell proliferation and autophagy in myopia and the associated retinopathy. Exp Eye Res. 2024 Apr;241:109829. doi: 10.1016/j.exer.2024.109829. Epub 2024 Feb 12. PMID: 38354943.
Wei X, Wang Y, Lao Y, Weng J, Deng R, Li S, Lu J, Yang S, Liu X. Effects of honokiol protects against chronic kidney disease via BNIP3/NIX and FUNDC1-mediated mitophagy and AMPK pathways. Mol Biol Rep. 2023 Aug;50(8):6557-6568. doi: 10.1007/s11033-023-08592-1. Epub 2023 Jun 20. PMID: 37338733.
Su L, Zhang J, Gomez H, Kellum JA, Peng Z. Mitochondria ROS and mitophagy in acute kidney injury. Autophagy. 2023 Feb;19(2):401-414. doi: 10.1080/15548627.2022.2084862. Epub 2022 Jun 9. PMID: 35678504; PMCID: PMC9851232.
Niemi NM, Friedman JR. Coordinating BNIP3/NIX-mediated mitophagy in space and time. Biochem Soc Trans. 2024 Oct 30;52(5):1969-1979. doi: 10.1042/BST20221364. PMID: 39377319; PMCID: PMC11555697.
Yang T, Hu J, Zhang L, Liu L, Pan X, Zhou Y, Wu Y, Shi X, Obiegbusi CN, Dong X. CircCUL1 inhibits trophoblast cell migration and invasion and promotes cell autophagy by sponging hsa-miR-30e-3p in fetal growth restriction via the ANXA1/PI3K/AKT axis. J Biochem Mol Toxicol. 2024 Jul;38(7):e23759. doi: 10.1002/jbt.23759. PMID: 39003567.
Pedersen T, Peters H. Proposal for a classification of oocytes and follicles in the mouse ovary. J Reprod Fertil 1968;17. https://doi.org/10.1530/jrf.0.0170555.
Miao C, Zhao Y, Chen Y, Wang R, Ren N, Liu Q, Dou X, Zhang Q. He's Yangchao recipe improves premature ovarian insufficiency by regulating mitochondrial biogenesis of granulose cells via ERβ/PGC1α/TFAM pathway. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2024 Mar 29;53(3):358-367. English, Chinese. doi: 10.3724/zdxbyxb-2023-0521. PMID: 39188182; PMCID: PMC11348690.
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.
Boros E, Elilié Mawa Ongoth F, Heinrichs C, Mansbach AL, Seneca S, Aeby A, et al. Primary ovarian insufficiency in RMND1 mitochondrial disease. Mitochondrion 2022;66:51–3. https://doi.org/10.1016/j.mito.2022.07.004.
Turkieh A, el Masri Y, Pinet F, Dubois-Deruy E. Mitophagy Regulation following Myocardial Infarction. Cells 2022;11. https://doi.org/10.3390/cells11020199.
Liu Z, Li C, Chen Q, Bai C, Wu G, Fu C, He T, Shen M, Feng C, Liu H. Follicular fluid meiosis-activating sterol prevents porcine ovarian granulosa cells from hypoxia-induced apoptosis via inhibiting STAT4 expression. J Anim Sci. 2024 Jan 3;102:skae125. doi: 10.1093/jas/skae125. PMID: 38713167; PMCID: PMC11245709.
Liu Z, Cui Z, Li C, Lu K, Chen K, Cui W, Wu Y, Xia D. Exposure to perfluorodecanoic acid impairs follicular development via inducing granulosa cell necroptosis. Ecotoxicol Environ Saf. 2024 Nov 15;287:117268. doi: 10.1016/j.ecoenv.2024.117268. Epub 2024 Nov 15. PMID: 39547057.
Pereira LAAC, Ferreira CS, Dias KSSA, Nogueira JM, Pinto FCH, Jorge EC, Campos-Junior PHA. Ovarian Puncture Triggers an Inflammatory Response that did not Affect Late Folliculogenesis, Ovulation Rate, and Fertility. Reprod Sci. 2024 Oct;31(10):3202-3214. doi: 10.1007/s43032-024-01654-0. Epub 2024 Jul 23. PMID: 39043998.
Kalich-Philosoph L, Roness H, Carmely A, Fishel-Bartal M, Ligumsky H, Paglin S, et al. Cyclophosphamide triggers follicle activation and "burnout "; AS101 prevents follicle loss and preserves fertility. Sci Transl Med 2013;5. https://doi.org/10.1126/scitranslmed.3005402.
Zhou L, Xie Y, Li S, Liang Y, Qiu Q, Lin H, et al. Rapamycin Prevents cyclophosphamide-induced Over-activation of Primordial Follicle pool through PI3K/Akt/mTOR Signaling Pathway in vivo. J Ovarian Res 2017;10. https://doi.org/10.1186/s13048-017-0350-3.
Qin S, Chi X, Zhu Z, Chen C, Zhang T, He M, Gao M, Zhao T, Zhang J, Zhang L, Zheng W, Chen Z, Wang W, Zhou B, Xia G, Wang C. Oocytes maintain low ROS levels to support the dormancy of primordial follicles. Aging Cell. 2025 Jan;24(1):e14338. doi: 10.1111/acel.14338. Epub 2024 Sep 19. PMID: 39297300; PMCID: PMC11709087.
Melekoglu R, Ciftci O, Eraslan S, Cetin A, Basak N. Beneficial effects of curcumin and capsaicin on cyclophosphamide-induced premature ovarian failure in a rat model. J Ovarian Res 2018;11. https://doi.org/10.1186/s13048-018-0409-9.
Jin M, Liu Z, Shi R, Deng Y, Lin J, Zhang Y, Lin L, Wang Y, Shi Y, Li C, Liu Z. Disrupted Mitochondrial Dynamics Impair Corneal Epithelial Healing in Neurotrophic Keratopathy. Int J Mol Sci. 2025 Feb 3;26(3):1290. doi: 10.3390/ijms26031290. PMID: 39941058; PMCID: PMC11818347.
Yang P, Fan M, Chen Y, Yang D, Zhai L, Fu B, Zhang L, Wang Y, Ma R, Sun L. A novel strategy for the protective effect of ginsenoside Rg1 against ovarian reserve decline by the PINK1 pathway. Pharm Biol. 2025 Dec;63(1):68-81. doi: 10.1080/13880209.2025.2453699. Epub 2025 Jan 25. PMID: 39862058; PMCID: PMC11770866.
Liu Y, Huang W, Wen J, Xiong X, Xu T, Wang Q, Chen X, Zhao X, Li S, Li X, Yang W. Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles. Neural Regen Res. 2025 Apr 1;20(4):1124-1134. doi: 10.4103/NRR.NRR-D-23-01140. Epub 2024 May 17. PMID: 38989951; PMCID: PMC11438320.
Zhang L, Yang S, Cui H, Hang C, Wang X, An L, Shan Z, Liang Z, Shao R, Tang Z. Hypothermia regulates mitophagy and apoptosis via PINK1/Parkin-VDAC 3 signaling pathway during oxygen-glucose deprivation/recovery injury. Sci Rep. 2025 Feb 7;15(1):4607. doi: 10.1038/s41598-025-89176-w. PMID: 39920327; PMCID: PMC11806084.
Yang Z, Yoshii SR, Sakai Y, Zhang J, Chino H, Knorr RL, Mizushima N. Autophagy adaptors mediate Parkin-dependent mitophagy by forming sheet-like liquid condensates. EMBO J. 2024 Nov;43(22):5613-5634. doi: 10.1038/s44318-024-00272-5. Epub 2024 Oct 17. PMID: 39420095; PMCID: PMC11574277.
Ortega-Domínguez B, Aparicio-Trejo OE, García-Arroyo FE, León-Contreras JC, Tapia E, Molina-Jijón E, et al. Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic. Food and Chemical Toxicology 2017;107. https://doi.org/10.1016/j.fct.2017.07.018.
Yan ZX, Zheng Z, Xue W, Zhao MZ, Fei XC, Wu LL, et al. MicroRNA181a Is overexpressed in t-cell leukemia/lymphoma and related to chemoresistance. Biomed Res Int 2015;2015. https://doi.org/10.1155/2015/197241.
Zhang C, Shen J, Kong S, Zhang M, Zhang Q, Zhou J, Zhen X, Kang N, Jiang Y, Ding L, Sun H, Yan G. MicroRNA-181a promotes follicular granulosa cell apoptosis via sphingosine-1-phosphate receptor 1 expression downregulation†. Biol Reprod. 2019 Nov 21;101(5):975-985. doi: 10.1093/biolre/ioz135. PMID: 31359035.
Chevalier FP, Rorteau J, Ferraro S, Martin LS, Gonzalez-Torres A, Berthier A, et al. MiR-30a-5p Alters Epidermal Terminal Differentiation during Aging by Regulating BNIP3L/NIX-Dependent Mitophagy. Cells 2022;11. https://doi.org/10.3390/cells11050836.
Harris TJ, Liao Y, Shi W, Evangelista M, Pal B, Puthalakath H, Aston R, Mollard R, Mariadason JM, Lee EF, Fairlie WD. Induction of endoplasmic reticulum stress is associated with the anti-tumor activity of monepantel across cancer types. Cancer Med. 2023 Jun;12(12):13522-13537. doi: 10.1002/cam4.6021. Epub 2023 May 6. PMID: 37148543; PMCID: PMC10315739.
Beigl TB, Paul A, Fellmeth TP, Nguyen D, Barber L, Weller S, Schäfer B, Gillissen BF, Aulitzky WE, Kopp HG, Rehm M, Andrews DW, Pluhackova K, Essmann F. BCL-2 and BOK regulate apoptosis by interaction of their C-terminal transmembrane domains. EMBO Rep. 2024 Sep;25(9):3896-3924. doi: 10.1038/s44319-024-00206-6. Epub 2024 Jul 24. PMID: 39048751; PMCID: PMC11387410.
Osterlund EJ, Hirmiz N, Nguyen D, Pemberton JM, Fang Q, Andrews DW. Endoplasmic reticulum protein BIK binds to and inhibits mitochondria-localized antiapoptotic proteins. J Biol Chem. 2023 Feb;299(2):102863. doi: 10.1016/j.jbc.2022.102863. Epub 2023 Jan 2. PMID: 36603764; PMCID: PMC9932132.
Sitthisuk P, Innajak S, Poorahong W, Samosorn S, Dolsophon K, Watanapokasin R. Effect of Acacia concinna Extract on Apoptosis Induction Associated with Endoplasmic Reticulum Stress and Modulated Intracellular Signaling Pathway in Human Colon HCT116 Cancer Cells. Nutrients. 2024 Nov 1;16(21):3764. doi: 10.3390/nu16213764. PMID: 39519596; PMCID: PMC11547357.
Leytens A, Benítez-Fernández R, Jiménez-García C, Roubaty C, Stumpe M, Boya P, Dengjel J. Targeted proteomics addresses selectivity and complexity of protein degradation by autophagy. Autophagy. 2025 Feb;21(2):460-475. doi: 10.1080/15548627.2024.2396792. Epub 2024 Sep 20. PMID: 39245437; PMCID: PMC11759517.

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

Year 2025, Volume: 64 Issue: 4, 688 - 700, 08.12.2025

Duygu Uçar Kartal , Naci Kemal Kuşçu , Kemal Özbilgin , Muhammed Yusuf Pekmezci

https://doi.org/10.19161/etd.1704479

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

Cyclophosphamide , Curcumin , Quercetin , MiRNA , POI , Parkin , FUNDC1

References

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.
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.
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.
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.
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.
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.
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.
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.
Chon SJ, Umair Z, Yoon M-S. Premature Ovarian Insufficiency: Past, Present, and Future. Front Cell Dev Biol 2021;9. https://doi.org/10.3389/fcell.2021.672890.
Jiang B, Hong N, Zhang L, Xu B, He Q, Qian X, Li F, Dong F. MiR-181a-5p may regulate cell proliferation and autophagy in myopia and the associated retinopathy. Exp Eye Res. 2024 Apr;241:109829. doi: 10.1016/j.exer.2024.109829. Epub 2024 Feb 12. PMID: 38354943.
Wei X, Wang Y, Lao Y, Weng J, Deng R, Li S, Lu J, Yang S, Liu X. Effects of honokiol protects against chronic kidney disease via BNIP3/NIX and FUNDC1-mediated mitophagy and AMPK pathways. Mol Biol Rep. 2023 Aug;50(8):6557-6568. doi: 10.1007/s11033-023-08592-1. Epub 2023 Jun 20. PMID: 37338733.
Su L, Zhang J, Gomez H, Kellum JA, Peng Z. Mitochondria ROS and mitophagy in acute kidney injury. Autophagy. 2023 Feb;19(2):401-414. doi: 10.1080/15548627.2022.2084862. Epub 2022 Jun 9. PMID: 35678504; PMCID: PMC9851232.
Niemi NM, Friedman JR. Coordinating BNIP3/NIX-mediated mitophagy in space and time. Biochem Soc Trans. 2024 Oct 30;52(5):1969-1979. doi: 10.1042/BST20221364. PMID: 39377319; PMCID: PMC11555697.
Yang T, Hu J, Zhang L, Liu L, Pan X, Zhou Y, Wu Y, Shi X, Obiegbusi CN, Dong X. CircCUL1 inhibits trophoblast cell migration and invasion and promotes cell autophagy by sponging hsa-miR-30e-3p in fetal growth restriction via the ANXA1/PI3K/AKT axis. J Biochem Mol Toxicol. 2024 Jul;38(7):e23759. doi: 10.1002/jbt.23759. PMID: 39003567.
Pedersen T, Peters H. Proposal for a classification of oocytes and follicles in the mouse ovary. J Reprod Fertil 1968;17. https://doi.org/10.1530/jrf.0.0170555.
Miao C, Zhao Y, Chen Y, Wang R, Ren N, Liu Q, Dou X, Zhang Q. He's Yangchao recipe improves premature ovarian insufficiency by regulating mitochondrial biogenesis of granulose cells via ERβ/PGC1α/TFAM pathway. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2024 Mar 29;53(3):358-367. English, Chinese. doi: 10.3724/zdxbyxb-2023-0521. PMID: 39188182; PMCID: PMC11348690.
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.
Boros E, Elilié Mawa Ongoth F, Heinrichs C, Mansbach AL, Seneca S, Aeby A, et al. Primary ovarian insufficiency in RMND1 mitochondrial disease. Mitochondrion 2022;66:51–3. https://doi.org/10.1016/j.mito.2022.07.004.
Turkieh A, el Masri Y, Pinet F, Dubois-Deruy E. Mitophagy Regulation following Myocardial Infarction. Cells 2022;11. https://doi.org/10.3390/cells11020199.
Liu Z, Li C, Chen Q, Bai C, Wu G, Fu C, He T, Shen M, Feng C, Liu H. Follicular fluid meiosis-activating sterol prevents porcine ovarian granulosa cells from hypoxia-induced apoptosis via inhibiting STAT4 expression. J Anim Sci. 2024 Jan 3;102:skae125. doi: 10.1093/jas/skae125. PMID: 38713167; PMCID: PMC11245709.
Liu Z, Cui Z, Li C, Lu K, Chen K, Cui W, Wu Y, Xia D. Exposure to perfluorodecanoic acid impairs follicular development via inducing granulosa cell necroptosis. Ecotoxicol Environ Saf. 2024 Nov 15;287:117268. doi: 10.1016/j.ecoenv.2024.117268. Epub 2024 Nov 15. PMID: 39547057.
Pereira LAAC, Ferreira CS, Dias KSSA, Nogueira JM, Pinto FCH, Jorge EC, Campos-Junior PHA. Ovarian Puncture Triggers an Inflammatory Response that did not Affect Late Folliculogenesis, Ovulation Rate, and Fertility. Reprod Sci. 2024 Oct;31(10):3202-3214. doi: 10.1007/s43032-024-01654-0. Epub 2024 Jul 23. PMID: 39043998.
Kalich-Philosoph L, Roness H, Carmely A, Fishel-Bartal M, Ligumsky H, Paglin S, et al. Cyclophosphamide triggers follicle activation and "burnout "; AS101 prevents follicle loss and preserves fertility. Sci Transl Med 2013;5. https://doi.org/10.1126/scitranslmed.3005402.
Zhou L, Xie Y, Li S, Liang Y, Qiu Q, Lin H, et al. Rapamycin Prevents cyclophosphamide-induced Over-activation of Primordial Follicle pool through PI3K/Akt/mTOR Signaling Pathway in vivo. J Ovarian Res 2017;10. https://doi.org/10.1186/s13048-017-0350-3.
Qin S, Chi X, Zhu Z, Chen C, Zhang T, He M, Gao M, Zhao T, Zhang J, Zhang L, Zheng W, Chen Z, Wang W, Zhou B, Xia G, Wang C. Oocytes maintain low ROS levels to support the dormancy of primordial follicles. Aging Cell. 2025 Jan;24(1):e14338. doi: 10.1111/acel.14338. Epub 2024 Sep 19. PMID: 39297300; PMCID: PMC11709087.
Melekoglu R, Ciftci O, Eraslan S, Cetin A, Basak N. Beneficial effects of curcumin and capsaicin on cyclophosphamide-induced premature ovarian failure in a rat model. J Ovarian Res 2018;11. https://doi.org/10.1186/s13048-018-0409-9.
Jin M, Liu Z, Shi R, Deng Y, Lin J, Zhang Y, Lin L, Wang Y, Shi Y, Li C, Liu Z. Disrupted Mitochondrial Dynamics Impair Corneal Epithelial Healing in Neurotrophic Keratopathy. Int J Mol Sci. 2025 Feb 3;26(3):1290. doi: 10.3390/ijms26031290. PMID: 39941058; PMCID: PMC11818347.
Yang P, Fan M, Chen Y, Yang D, Zhai L, Fu B, Zhang L, Wang Y, Ma R, Sun L. A novel strategy for the protective effect of ginsenoside Rg1 against ovarian reserve decline by the PINK1 pathway. Pharm Biol. 2025 Dec;63(1):68-81. doi: 10.1080/13880209.2025.2453699. Epub 2025 Jan 25. PMID: 39862058; PMCID: PMC11770866.
Liu Y, Huang W, Wen J, Xiong X, Xu T, Wang Q, Chen X, Zhao X, Li S, Li X, Yang W. Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles. Neural Regen Res. 2025 Apr 1;20(4):1124-1134. doi: 10.4103/NRR.NRR-D-23-01140. Epub 2024 May 17. PMID: 38989951; PMCID: PMC11438320.
Zhang L, Yang S, Cui H, Hang C, Wang X, An L, Shan Z, Liang Z, Shao R, Tang Z. Hypothermia regulates mitophagy and apoptosis via PINK1/Parkin-VDAC 3 signaling pathway during oxygen-glucose deprivation/recovery injury. Sci Rep. 2025 Feb 7;15(1):4607. doi: 10.1038/s41598-025-89176-w. PMID: 39920327; PMCID: PMC11806084.
Yang Z, Yoshii SR, Sakai Y, Zhang J, Chino H, Knorr RL, Mizushima N. Autophagy adaptors mediate Parkin-dependent mitophagy by forming sheet-like liquid condensates. EMBO J. 2024 Nov;43(22):5613-5634. doi: 10.1038/s44318-024-00272-5. Epub 2024 Oct 17. PMID: 39420095; PMCID: PMC11574277.
Ortega-Domínguez B, Aparicio-Trejo OE, García-Arroyo FE, León-Contreras JC, Tapia E, Molina-Jijón E, et al. Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic. Food and Chemical Toxicology 2017;107. https://doi.org/10.1016/j.fct.2017.07.018.
Yan ZX, Zheng Z, Xue W, Zhao MZ, Fei XC, Wu LL, et al. MicroRNA181a Is overexpressed in t-cell leukemia/lymphoma and related to chemoresistance. Biomed Res Int 2015;2015. https://doi.org/10.1155/2015/197241.
Zhang C, Shen J, Kong S, Zhang M, Zhang Q, Zhou J, Zhen X, Kang N, Jiang Y, Ding L, Sun H, Yan G. MicroRNA-181a promotes follicular granulosa cell apoptosis via sphingosine-1-phosphate receptor 1 expression downregulation†. Biol Reprod. 2019 Nov 21;101(5):975-985. doi: 10.1093/biolre/ioz135. PMID: 31359035.
Chevalier FP, Rorteau J, Ferraro S, Martin LS, Gonzalez-Torres A, Berthier A, et al. MiR-30a-5p Alters Epidermal Terminal Differentiation during Aging by Regulating BNIP3L/NIX-Dependent Mitophagy. Cells 2022;11. https://doi.org/10.3390/cells11050836.
Harris TJ, Liao Y, Shi W, Evangelista M, Pal B, Puthalakath H, Aston R, Mollard R, Mariadason JM, Lee EF, Fairlie WD. Induction of endoplasmic reticulum stress is associated with the anti-tumor activity of monepantel across cancer types. Cancer Med. 2023 Jun;12(12):13522-13537. doi: 10.1002/cam4.6021. Epub 2023 May 6. PMID: 37148543; PMCID: PMC10315739.
Beigl TB, Paul A, Fellmeth TP, Nguyen D, Barber L, Weller S, Schäfer B, Gillissen BF, Aulitzky WE, Kopp HG, Rehm M, Andrews DW, Pluhackova K, Essmann F. BCL-2 and BOK regulate apoptosis by interaction of their C-terminal transmembrane domains. EMBO Rep. 2024 Sep;25(9):3896-3924. doi: 10.1038/s44319-024-00206-6. Epub 2024 Jul 24. PMID: 39048751; PMCID: PMC11387410.
Osterlund EJ, Hirmiz N, Nguyen D, Pemberton JM, Fang Q, Andrews DW. Endoplasmic reticulum protein BIK binds to and inhibits mitochondria-localized antiapoptotic proteins. J Biol Chem. 2023 Feb;299(2):102863. doi: 10.1016/j.jbc.2022.102863. Epub 2023 Jan 2. PMID: 36603764; PMCID: PMC9932132.
Sitthisuk P, Innajak S, Poorahong W, Samosorn S, Dolsophon K, Watanapokasin R. Effect of Acacia concinna Extract on Apoptosis Induction Associated with Endoplasmic Reticulum Stress and Modulated Intracellular Signaling Pathway in Human Colon HCT116 Cancer Cells. Nutrients. 2024 Nov 1;16(21):3764. doi: 10.3390/nu16213764. PMID: 39519596; PMCID: PMC11547357.
Leytens A, Benítez-Fernández R, Jiménez-García C, Roubaty C, Stumpe M, Boya P, Dengjel J. Targeted proteomics addresses selectivity and complexity of protein degradation by autophagy. Autophagy. 2025 Feb;21(2):460-475. doi: 10.1080/15548627.2024.2396792. Epub 2024 Sep 20. PMID: 39245437; PMCID: PMC11759517.

There are 40 citations in total.

Details

Primary Language	English
Subjects	Obstetrics and Gynaecology
Journal Section	Research Article
Authors	Duygu Uçar Kartal 0000-0003-4751-5944 Naci Kemal Kuşçu 0000-0002-7953-9361 Kemal Özbilgin 0000-0001-6627-5443 Muhammed Yusuf Pekmezci 0000-0003-1040-0393
Publication Date	December 8, 2025
Submission Date	May 22, 2025
Acceptance Date	August 28, 2025
Published in Issue	Year 2025 Volume: 64 Issue: 4

Cite

Vancouver	Uçar Kartal D, Kuşçu NK, Özbilgin K, Pekmezci MY. Effects of antioxidants used in the experimental premature ovarian insufficiency model on mitophagy proteins and them-associated MicroRNAs. EJM. 2025;64(4):688-700.

Download Cover Image

Article Files

Full Text

Ege Journal of Medicine enables the sharing of articles according to the Attribution-Non-Commercial-Share Alike 4.0 International (CC BY-NC-SA 4.0) license.