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Article

Mitophagy Protects Against Cisplatin-Induced Injury in Granulosa Cells

1
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230088, China
2
NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China
3
Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People’s Republic of China, Hefei 230032, China
4
Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases, Hefei 230032, China
5
Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei 230032, China
6
Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230031, China
*
Authors to whom correspondence should be addressed.
Toxics 2025, 13(5), 332; https://doi.org/10.3390/toxics13050332
Submission received: 20 March 2025 / Revised: 16 April 2025 / Accepted: 21 April 2025 / Published: 23 April 2025
(This article belongs to the Section Drugs Toxicity)

Abstract

Cisplatin, a widely used chemotherapeutic agent, is known to induce premature ovarian insufficiency (POI) and infertility in women of reproductive age. Among the contributing factors, cisplatin-induced apoptosis of ovarian granulosa cells is considered a primary driver of ovarian dysfunction; however, the underlying mechanisms remain incompletely understood. In this study, we investigated the cytotoxicity of cisplatin on the granulosa cell line KGN in vitro and explored the associated mechanisms. Our results demonstrate that cisplatin induces KGN cell apoptosis in a dose-dependent manner and impairs mitochondrial function, as evidenced by excessive ROS production, membrane potential collapse, and reduced ATP synthesis. Mitophagy, a key cellular self-protection mechanism that selectively removes damaged mitochondria, was activated following cisplatin treatment, mitigating its detrimental effects on KGN cells. Activation of mitophagy with urolithin A (UA) ameliorated cisplatin-induced mitochondrial dysfunction and apoptosis, whereas inhibition of mitophagy with cyclosporine A (CsA) exacerbated these effects. Furthermore, pretreatment with the clinical drug melatonin significantly enhanced mitophagy, effectively attenuating cisplatin-induced apoptosis in KGN cells. This study proposes a novel therapeutic strategy for patients undergoing tumor chemotherapy, aiming to preserve treatment efficacy while reducing the adverse effects of chemotherapeutic agents on ovarian function, thereby improving patients’ quality of life.
Keywords: cisplatin; mitophagy; apoptosis; KGN cells; melatonin cisplatin; mitophagy; apoptosis; KGN cells; melatonin

Share and Cite

MDPI and ACS Style

Zhu, S.; Tang, M.; Chen, J.; Li, S.; Xue, R. Mitophagy Protects Against Cisplatin-Induced Injury in Granulosa Cells. Toxics 2025, 13, 332. https://doi.org/10.3390/toxics13050332

AMA Style

Zhu S, Tang M, Chen J, Li S, Xue R. Mitophagy Protects Against Cisplatin-Induced Injury in Granulosa Cells. Toxics. 2025; 13(5):332. https://doi.org/10.3390/toxics13050332

Chicago/Turabian Style

Zhu, Sihui, Mingge Tang, Jiahua Chen, Shuhang Li, and Rufeng Xue. 2025. "Mitophagy Protects Against Cisplatin-Induced Injury in Granulosa Cells" Toxics 13, no. 5: 332. https://doi.org/10.3390/toxics13050332

APA Style

Zhu, S., Tang, M., Chen, J., Li, S., & Xue, R. (2025). Mitophagy Protects Against Cisplatin-Induced Injury in Granulosa Cells. Toxics, 13(5), 332. https://doi.org/10.3390/toxics13050332

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