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线粒体靶向策略提升卵巢冷冻保存效果:SS31 联合 rhGM-CSF 凝胶促进卵泡存活

Mitochondrial-targeted strategies for advancing ovarian cryopreservation: enhancing follicular survival and reproductive health

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研究将线粒体靶向抗氧化肽 elamipretide(SS31)与重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)凝胶联用,在兔卵巢移植部位实现 SS31 局部缓释。该组合通过降低氧化应激、改善线粒体功能提高卵泡存活,移植后 8 周恢复生殖内分泌功能,蛋白组与代谢组分析显示作用主要源于能量代谢通路激活。

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npj Regenerative Medicine (2026) Cite this article

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Abstract

Global fertility rates are in decline, underscoring the importance of effective fertility preservation strategies. Ovarian tissue cryopreservation and transplantation (OTCT) shows great promise but faces challenges like oxidative stress, ischemia-reperfusion injury, and poor follicle survival due to burn out. Protecting and preserving a greater number of primordial follicles remains pivotal to the success of this technology. While current strategies predominantly rely on antioxidants, their efficacy is constrained by non-specificity and the inability to achieve sustained release at the transplantation site. In this study, we explored the potential of elamipretide (SS31), a novel mitochondrial-targeted antioxidant peptide, to address these limitations. By combining SS31 with a recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) gel, we achieved localized and sustained release of SS31 at the transplantation site in rabbits. This combination demonstrated synergistic effects by reducing oxidative stress, improving mitochondrial function, and enhancing follicular survival. Notably, reproductive endocrine function was restored 8 weeks post-transplantation. Proteomics and metabolomics analyses revealed that these improvements were primarily attributed to the activation of energy metabolism pathway. Our findings suggest improved transplantation outcomes in preclinical settings, highlighting the potential of this strategy to serve as an efficient and precise approach for women requiring urgent fertility preservation in the future.

Acknowledgements

The authors would like to express their sincere gratitude to Dr. Jun Chang for technical support during the ovarian transplantation surgery.

Funding

This work was supported by The Sichuan Provincial Science and Technology Program (No. 2024NSFSC1678), Medical Youth Innovation Research Project of Sichuan Province(No. Q23064); Science and Technology Research Special Project of Sichuan Provincial Administration of Traditional Chinese Medicine(25MSZX528); The Central Government Guides Local Science and Technology Development Fund Projects (No. 2023ZYD0116); Sichuan Provincial Cadre Health Research Project (Grant No. 2024-2201); the Key Medical Science and Technology Research and Development Project of Sichuan Provincial Health Commission (No. 21ZD009), Medical Research Project of Sichuan Medical Association (No. S23027); Sichuan Provincial Key Laboratory/Center for Development and Regeneration (No. 24LHFYSZ1-01).

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Author notes

  1. These authors contributed equally: Qin Zeng, Kai Wang, Guohui Zhang, Yangbao Miao.

Authors and Affiliations

  1. Key Laboratory of Reproductive Medicine, Sichuan Provincial Maternity and Child Health Care Hospital, Sichuan Provincial Women’s and Children’s Hospital, The Affiliated Women’s and children’s Hospital of Chengdu Medical College, Chengdu, China

    Qin Zeng, Guohui Zhang, Dongsheng Xiong, Ling Yu, Libing He, Li Wang, Rong Li, Jiuzhi Zeng & Weixin Liu

  2. Department of Acute Care Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China

    Kai Wang

  3. Department of Haematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’ s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China

    Yangbao Miao

  4. College of Natural Sciences, The University of Texas at Austin, Austin, TX, USA

    Yunchang Luo

  5. School of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China

    Xinrong Du, Jun Liu, Min Jiang, Ningjing Li, Changli Han & Weixin Liu

  6. School of Clinical Laboratory Medicine, Chengdu Medical College, Chengdu, China

    Yuhong Zhao & Heqiu Yan

  7. Department of Obstetrics and Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, China

    Wenming Xu

Authors

  1. Qin Zeng
  2. Kai Wang
  3. Guohui Zhang
  4. Yangbao Miao
  5. Yunchang Luo
  6. Dongsheng Xiong
  7. Ling Yu
  8. Libing He
  9. Li Wang
  10. Xinrong Du
  11. Jun Liu
  12. Rong Li
  13. Min Jiang
  14. Yuhong Zhao
  15. Ningjing Li
  16. Changli Han
  17. Heqiu Yan
  18. Jiuzhi Zeng
  19. Wenming Xu
  20. Weixin Liu

Corresponding authors

Correspondence to Jiuzhi Zeng, Wenming Xu or Weixin Liu.

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Competing interests

The authors declare no competing interests.

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Cite this article

Zeng, Q., Wang, K., Zhang, G. et al. Mitochondrial-targeted strategies for advancing ovarian cryopreservation: enhancing follicular survival and reproductive health. npj Regen Med (2026). https://doi.org/10.1038/s41536-026-00521-7

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  • Received: 07 January 2025

  • Accepted: 01 October 2026

  • Published: 28 October 2026

  • DOI: https://doi.org/10.1038/s41536-026-00521-7

来源:Nature Biotechnology · nature.com

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