2. Academic Validation
  3. Serine inhibits granulosa cell ferroptosis to maintain ovarian function

Serine inhibits granulosa cell ferroptosis to maintain ovarian function

  • Nat Commun. 2026 Jan 21;17(1):1738. doi: 10.1038/s41467-026-68440-1.
Hao-Cheng Gu # 1 2 3,  You-Qiong Zhuo # 2 4,  Ling-Fang Wang # 2,  Yu-Wei Zhang 2 3,  Dong-Shui Li 5,  Ling-Qin Chen 5,  Zhi-Hua Li 6 7,  Yun-Yue Wang 6 7,  Yi-Kai Wang 1 2,  Hui-Ting Liao 2,  Jia-Qin Wu 2 3,  Shi-Qing Tao 2 3,  Xing-Yu Wei 2,  Ke-Yu Deng 8 9 10,  Hong-Bo Xin 11 12 13 14
Affiliations

Affiliations

  • 1 School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China.
  • 2 The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Province Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China.
  • 3 School of Life and Science, Nanchang University, Nanchang, P. R. China.
  • 4 School of Food Science and Technology, Nanchang University, Nanchang, P. R. China.
  • 5 Department of Assisted Reproduction, The First Affiliated Hospital of Nanchang University, Nanchang, P. R. China.
  • 6 Department of Breast Surgery, Third Hospital of Nanchang, Jiangxi Breast Specialist Hospital, Nanchang, P.R. China.
  • 7 Jiangxi Province Key Laboratory of Breast Diseases, Third Hospital of Nanchang, Nanchang, P.R. China.
  • 8 School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China. [email protected].
  • 9 The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Province Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China. [email protected].
  • 10 School of Life and Science, Nanchang University, Nanchang, P. R. China. [email protected].
  • 11 School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China. [email protected].
  • 12 The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Province Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China. [email protected].
  • 13 School of Life and Science, Nanchang University, Nanchang, P. R. China. [email protected].
  • 14 School of Food Science and Technology, Nanchang University, Nanchang, P. R. China. [email protected].
  • # Contributed equally.
PMID: 41565641 DOI: 10.1038/s41467-026-68440-1
Abstract

Cyclophosphamide (CTX) is a primary medicine for curing breast Cancer which often causes premature ovarian insufficiency (POI). Our recent publication reveals that CTX induces POI by promoting the expression of SLC1A4, a transporter of serine efflux, in ovarian granulosa cells (GCs). Here, we report that there is a closed connection between the reduction of serum serine and ovarian hypofunction in the breast Cancer patients treated with CTX or women of childbearing age who are suffered from the staying-up-late. Additionally, we observe that dietary serine supplementation protects mice from CTX-induced POI without altering its anti-breast Cancer. Furthermore, we demonstrate that the elevated serine promotes S1P synthesis, and in turn, inhibits the nuclear translocation of Nrf2 and consequent HO-1 expression, to suppress Ferroptosis in GCs. Our study reveals that the chemotherapy-induced or idiopathic POI share the same mechanisms, indicating that serine is a critical factor for maintaining ovarian function.

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