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Peer-reviewedCC BY 4.0Cell Death Discovery

Ketamine improves ovarian function and oocyte quality in CORT-induced depression mouse model by ferroptosis pathway

  • Yuqing Liu1
  • Jiang Jiang1,2
  • Yalong Wang1,3
  • Zhaocheng Zeng1,2
  • Liying Zhou1,4
  • Zhiqin Li5
  • Bin Deng6
  • Jinling Wang7
  • Hailong Wang1
7 affiliations
  1. 1Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen, China
  2. 2Reproductive Medical Center, Zhanjiang Jiuhe Hospital, Zhanjiang, China
  3. 3Center for Reproductive Medicine, Maternity and Child Health Care Hospital in Xiangtan, Xiangtan, China
  4. 4Reproductive Medicine Center, Xiamen University Affiliated Chenggong Hospital, Xiamen, China
  5. 5Department of Anesthesiology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
  6. 6Department of Anesthesiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
  7. 7Department of Emergency and Critical Care Center, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Zhanjiang, China
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Abstract

Depression is a common psychiatric disorder, with a higher prevalence in women than in men, and has been increasingly associated with disturbances in female reproductive health. In particular, depressive conditions may impair ovarian function and compromise oocyte quality, thereby contributing to reproductive disorders. Ketamine is a clinically effective antidepressant. However, its potential role in improving depression-induced female reproductive disorders remains unclear. In the present study, a corticosterone (CORT)-induced mouse model of depression was used to evaluate whether ketamine could ameliorate ovarian dysfunction and oocyte impairment. Ketamine treatment significantly improved depressive-like behaviors and partially reversed abnormalities in ovarian function and oocyte quality. Metabolomics and single-cell transcriptomics analyses suggested that ketamine may enhance oocyte quality in depressive mice through the regulation of ferroptosis. Our findings confirmed that ketamine ameliorated alterations in ROS, Fe2+, glutathione (GSH), and lipid peroxidation levels in oocytes, reduced ovarian mitochondrial abnormalities, and regulated the ferroptosis-related proteins GPX4, FTH1, and FTL in ovarian tissues. In conclusion, ketamine alleviates depression-associated ovarian dysfunction and oocyte impairment, potentially through modulation of ferroptotic signaling, offering new insights linking mental disorders to female reproductive health.

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Cite

BibTeXRIS
BibTeX
@article{liu2026ketamine,
  title = {{Ketamine improves ovarian function and oocyte quality in CORT-induced depression mouse model by ferroptosis pathway}},
  author = {Yuqing Liu and Jiang Jiang and Yalong Wang and Zhaocheng Zeng and Liying Zhou and Zhiqin Li and Bin Deng and Jinling Wang and Hailong Wang},
  journal = {Cell Death Discovery},
  year = {2026},
  month = aug,
  doi = {10.1038/s41420-026-03291-9},
  url = {https://doi.org/10.1038/s41420-026-03291-9},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Ketamine improves ovarian function and oocyte quality in CORT-induced depression mouse model by ferroptosis pathway
AU  - Yuqing Liu
AU  - Jiang Jiang
AU  - Yalong Wang
AU  - Zhaocheng Zeng
AU  - Liying Zhou
AU  - Zhiqin Li
AU  - Bin Deng
AU  - Jinling Wang
AU  - Hailong Wang
PY  - 2026
DA  - 2026/08/08
JO  - Cell Death Discovery
DO  - 10.1038/s41420-026-03291-9
UR  - https://doi.org/10.1038/s41420-026-03291-9
AB  - Depression is a common psychiatric disorder, with a higher prevalence in women than in men, and has been increasingly associated with disturbances in female reproductive health. In particular, depressive conditions may impair ovarian function and compromise oocyte quality, thereby contributing to reproductive disorders. Ketamine is a clinically effective antidepressant. However, its potential role in improving depression-induced female reproductive disorders remains unclear. In the present study, a corticosterone (CORT)-induced mouse model of depression was used to evaluate whether ketamine could ameliorate ovarian dysfunction and oocyte impairment. Ketamine treatment significantly improved depressive-like behaviors and partially reversed abnormalities in ovarian function and oocyte quality. Metabolomics and single-cell transcriptomics analyses suggested that ketamine may enhance oocyte quality in depressive mice through the regulation of ferroptosis. Our findings confirmed that ketamine ameliorated alterations in ROS, Fe2+, glutathione (GSH), and lipid peroxidation levels in oocytes, reduced ovarian mitochondrial abnormalities, and regulated the ferroptosis-related proteins GPX4, FTH1, and FTL in ovarian tissues. In conclusion, ketamine alleviates depression-associated ovarian dysfunction and oocyte impairment, potentially through modulation of ferroptotic signaling, offering new insights linking mental disorders to female reproductive health.
SN  - 2058-7716
ER  -