Mitochondria-targeted peptide elamipretide alleviates cisplatin-induced ovarian failure by activating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway.
7 affiliations
- 1Center of Women's and Children's Health Medical Research and Technology Innovation, Sichuan Provincial Women's and Children's Hospital/The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu, China.
- 2Key Laboratory of Fertility Preservation and Promotion, Sichuan Provincial Women's and Children's Hospital/The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu, China.
- 3Key Laboratory for Minimally Invasive/Non-Invasive Diagnosis and Treatment of Female Reproductive System Diseases and Lifelong Reproductive Health Protection, Sichuan Provincial Women's and Children's Hospital/The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu, China.
- 4College of Laboratory Medicine, Chengdu Medical College, Chengdu, China.
- 5Reproductive Laboratory, Meishan Women and Children's Hospital, Alliance Hospital of West China Second University Hospital, Meishan, China.
- 6School of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
- 7Key Laboratory of Reproductive Medicine, Sichuan Provincial Women's and Children's Hospital/The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu, China.
Abstract
Background
Premature ovarian failure (POF) is a complex endocrine disorder that severely impairs female fertility. Cisplatin, a commonly used chemotherapeutic agent, has been identified as a major risk factor for POF in young women. This study aimed to investigate the protective effects and underlying mechanisms of the mitochondria-targeted peptide elamipretide (SS31) in a cisplatin-induced mouse model of POF.Methods
POF was established via intraperitoneal cisplatin (2 mg/kg, 7 days), followed by SS31 treatment (10 mg/kg, 3 weeks).Results
SS31 treatment significantly alleviated cisplatin-induced ovarian damage and reversed key pathological features of POF. Mice treated with SS31 exhibited more rapid recovery in body weight, increased ovarian size and weight, improved ovarian morphology, and a significantly higher number of follicles at various developmental stages compared to the model group. SS31 also normalized serum hormone levels, reduced oxidative stress, restored mitochondrial membrane potential, and improved mitochondrial morphology in oocytes and granulosa cells. Mechanistically, SS31 activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in ovarian tissues.Conclusion
The mitochondria-targeted peptide SS31 effectively ameliorates cisplatin-induced POF in mice by enhancing antioxidant defenses and preserving mitochondrial function. These findings suggest that SS31 is a promising therapeutic candidate for the clinical management of POF and provide new insights into antioxidant-based interventions.
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BibTeX
@article{zhao2026mitochondriatargeted,
title = {{Mitochondria-targeted peptide elamipretide alleviates cisplatin-induced ovarian failure by activating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway.}},
author = {Yuhong Zhao and Heqiu Yan and Li Wang and Yu Lei and Ningjing Li and Jun Liu and Xia Bai and Weiwei Zhi and Min Jiang and Li Li and Guohui Zhang and Weixin Liu},
journal = {Frontiers in pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1960111},
url = {https://europepmc.org/article/MED/42898512},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mitochondria-targeted peptide elamipretide alleviates cisplatin-induced ovarian failure by activating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway.
AU - Yuhong Zhao
AU - Heqiu Yan
AU - Li Wang
AU - Yu Lei
AU - Ningjing Li
AU - Jun Liu
AU - Xia Bai
AU - Weiwei Zhi
AU - Min Jiang
AU - Li Li
AU - Guohui Zhang
AU - Weixin Liu
PY - 2026
DA - 2026/10/05
JO - Frontiers in pharmacology
DO - 10.3389/fphar.2026.1960111
UR - https://europepmc.org/article/MED/42898512
AB - Background Premature ovarian failure (POF) is a complex endocrine disorder that severely impairs female fertility. Cisplatin, a commonly used chemotherapeutic agent, has been identified as a major risk factor for POF in young women. This study aimed to investigate the protective effects and underlying mechanisms of the mitochondria-targeted peptide elamipretide (SS31) in a cisplatin-induced mouse model of POF.Methods POF was established via intraperitoneal cisplatin (2 mg/kg, 7 days), followed by SS31 treatment (10 mg/kg, 3 weeks).Results SS31 treatment significantly alleviated cisplatin-induced ovarian damage and reversed key pathological features of POF. Mice treated with SS31 exhibited more rapid recovery in body weight, increased ovarian size and weight, improved ovarian morphology, and a significantly higher number of follicles at various developmental stages compared to the model group. SS31 also normalized serum hormone levels, reduced oxidative stress, restored mitochondrial membrane potential, and improved mitochondrial morphology in oocytes and granulosa cells. Mechanistically, SS31 activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in ovarian tissues.Conclusion The mitochondria-targeted peptide SS31 effectively ameliorates cisplatin-induced POF in mice by enhancing antioxidant defenses and preserving mitochondrial function. These findings suggest that SS31 is a promising therapeutic candidate for the clinical management of POF and provide new insights into antioxidant-based interventions.
SN - 1663-9812
ER -