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Unraveling the Clinical Relevance of Ferroptosis-Related Genes in Human Ovarian Aging

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Abstract

Ferroptosis, a recently discovered form of cell death, has been implicated in various diseases. However, the genetic relationship between ferroptosis and ovarian aging has not been thoroughly investigated through informatics analysis. In this study, we conducted bioinformatics analysis using ovarian aging and ferroptosis datasets to identify potential ferroptosis-related genes using R software. The expression levels of these genes at different ages were analyzed using the GTEx public database. To validate these findings at the genetic level, we performed clinical infertility biopsies. Bioinformatics analysis of a mouse ovary dataset revealed significantly higher expression of Tfrc, Ncoa4, and Slc3a2 in the aging group compared to the young group, while Gpx4 showed the opposite pattern. Consistent results were observed in biopsies from clinically aged infertile patients. This study is the first to identify a ferroptosis-related gene associated with ovarian aging, highlighting its potential as a diagnostic biomarker.

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Funding

This research was funded by the Ministry of Science Technology (MOST 111–2314-B-075B-014-MY3, 111–2314-B-075B-004-MY3), Kaohsiung Veterans General Hospital (VGHKS111-144, 111–145, 111–147, and 111-D06-1), and Yen Tjing Ling Medical Foundation (CI-111–16 and CI-112–10).

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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

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

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

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

  4. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan

    Wan-Ping Su, Jim Jinn-Chyuan Sheu & Kuan-Hao Tsui

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

    Zhi-Hong Wen

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

    Kuan-Hao Tsui

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

    Kuan-Hao Tsui

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

    Kuan-Hao Tsui

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  1. Pei-Hsuan Lin
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Corresponding authors

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

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Ethics Approval

This study was approved by the Institutional Review Board of the Kaohsiung Veterans General Hospital (KSVGH21-CT1-43). All procedures conducted in this study were in accordance with the principles stated in the Declaration of Helsinki.

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Highlights

• Identification of ferroptosis-related genes as diagnostic markers for ovarian aging.

• Predictive value of ferroptosis-related genes in infertility patients.

• Clinical biopsy validates the link between ferroptosis-related genes and ovarian aging.

• Ferroptosis-related genes as potential biomarkers for ovarian aging.

• The role of ferroptosis-related genes in assessing ovarian aging through clinical biopsy.

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Lin, PH., Li, CJ., Lin, LT. et al. Unraveling the Clinical Relevance of Ferroptosis-Related Genes in Human Ovarian Aging. Reprod. Sci. 30, 3529–3536 (2023). https://doi.org/10.1007/s43032-023-01310-z

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  • DOI: https://doi.org/10.1007/s43032-023-01310-z

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