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Cuproptosis-Related Gene FDX1 Identified as a Potential Target for Human Ovarian Aging

  • Reproductive Biology: Original Article
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Abstract

Cuproptosis is a recently discovered mode of cell death that has garnered attention due to its association with various diseases. However, the intricate genetic relationship between cuproptosis and ovarian aging has remained largely unexplored. This study aimed to bridge this knowledge gap by leveraging data sets related to ovarian aging and cuproptosis. Through comprehensive bioinformatics analyses, facilitated by R software, we uncovered FDX1 as a potential cuproptosis-related gene with relevance to ovarian aging. To gain insights into FDX1's role, we conducted spatial transcriptome analyses in the ovaries of both young and aged female mice. These experiments revealed a significant reduction in FDX1 expression in the aging group compared to the young group. To substantiate these findings at the genetic level, we turned to clinical infertility biopsies. Impressively, we observed consistent results in biopsies from elderly infertile patients, reinforcing the link between FDX1 and ovarian aging. Moreover, we delved into the pharmacogenomics of ovarian cell lines and discovered that FDX1 expression levels were intricately associated with heightened sensitivity to specific small molecule drugs. This observation suggests that modulating FDX1 could potentially be a strategy to influence drug responses in ovarian-related therapies. In sum, this study marks a pioneering effort in identifying FDX1 as a cuproptosis-related gene implicated in ovarian aging. These findings hold substantial promise, not only in shedding light on the underlying mechanisms of ovarian aging but also in positioning FDX1 as a potential diagnostic biomarker and therapeutic target. With further research, FDX1 could play a pivotal role in advancing precision medicine and therapies for ovarian-related conditions.

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Acknowledgements

We thank Ching-Yu Chu for supporting data collection and statistical analysis.

Author information

Author notes

  1. Chia-Chun Wu

    Present address: Institute of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan

  2. Chia-Jung Li

    Present address: Institute of Biopharmaceutical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan

  3. Lin Li-Te

    Present address: Department of Obstetrics and Gynaecology, National Yang-Ming University School of Medicine, Taipei, 112, Taiwan

  4. Zhi-Hong Wen

    Present address: Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan

Authors and Affiliations

  1. Institute of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan

    Pei-Hsuan Lin, Jiin-Tsuey Cheng & Kuan-Hao Tsui

  2. Department of Obstetrics and Gynaecology, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan

    Chia-Jung Li, Lin Li-Te, Pei-Hsuan Lin & Kuan-Hao Tsui

  3. Institute of Biopharmaceutical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan

    Lin Li-Te & Kuan-Hao Tsui

  4. Department of Obstetrics and Gynaecology, National Yang-Ming University School of Medicine, Taipei, 112, Taiwan

    Kuan-Hao Tsui

  5. Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan

    Kuan-Hao Tsui

  6. Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, 112, Taiwan

    Kuan-Hao Tsui

  7. Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan

    Kuan-Hao Tsui

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  1. Chia-Chun Wu
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Contributions

Conceptualization, C.-J.L., Z.-H.W. and L.-T.L.; Methodology, C.-J.L.; Formal Analysis, C.-C.W. and L.-T.L.; Writing-Original Draft Preparation, C.-C.W., J.-T.C.; Writing-Review & Editing, J.-T.C. and K.-H.T.; Supervision, K.-H.T.

Corresponding authors

Correspondence to Jiin-Tsuey Cheng or Kuan-Hao Tsui.

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Formatting of funding sources

This research was funded by the Ministry of Science Technology (MOST 111–2314-B-075B-014-MY3) and Kaohsiung Veterans General Hospital (VGHKS111-144, 112–089 and 112-D07).

Conflicts of Interest

The authors declare no conflict of interest.

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Highlights

• Identification of Cuproptosis-Related Genes as Diagnostic Markers for Ovarian Aging

• Predictive Value of Cuproptosis-Related Genes in Infertility Patients

• Clinical Biopsy Validates the Link Between Cuproptosis-Related Genes and Ovarian Aging

• Cuproptosis-Related Genes as Potential Biomarkers for Ovarian Aging

• The Role of Cuproptosis-Related Genes in Assessing Ovarian Aging through Clinical Biopsy

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Supplementary file1 (DOCX 15 KB)

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Wu, CC., Li, CJ., Lin, LT. et al. Cuproptosis-Related Gene FDX1 Identified as a Potential Target for Human Ovarian Aging. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01573-0

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  • DOI: https://doi.org/10.1007/s43032-024-01573-0

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