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  3. Cadmium exposure is associated with impaired ovarian function: Potential role of cadmium-induced ferroptosis in granulosa cells

Cadmium exposure is associated with impaired ovarian function: Potential role of cadmium-induced ferroptosis in granulosa cells

  • J Hazard Mater. 2026 Feb 1:503:141148. doi: 10.1016/j.jhazmat.2026.141148.
Jing Li 1,  Yutong Wang 2,  Yali Huang 1,  Nidong Li 1,  Yingxin Zhu 1,  Shengli Lin 1,  Linlin Wang 1,  Wei Guo 1,  Lailai Yan 3,  Chan Tian 4,  Ying Wang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China.
  • 2 Center for Reproductive Medicine, the Affiliated Hospital of Inner Mongolia Medical University, China.
  • 3 Central Laboratory of School of Public Health, Peking University, Beijing 100191, China.
  • 4 State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China; Department of Medical Genetics, Peking University, Beijing 100191, China; School of Basic Medical Sciences, Peking University, Beijing 100191, China. Electronic address: [email protected].
  • 5 State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China. Electronic address: [email protected].
PMID: 41548307 DOI: 10.1016/j.jhazmat.2026.141148
Abstract

Cadmium (Cd) is a toxic environmental heavy metal with potential toxicity on the reproductive system. Cd-induced effects on ovarian function and the underlying mechanisms are unclear. This study integrated population-based and in vitro experiments to investigate the associations between environmental Cd exposure and ovarian dysfunction in reproductive-age women with infertility, and elucidated the potential molecular mechanisms involved. Elevated Cd exposure was significantly associated with lower serum estradiol levels and an inverted U-shaped relationship with anti-Müllerian hormone levels, suggesting diminished ovarian reserve. No significant associations were observed between Cd concentrations and in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) pregnancy outcomes. In vitro, Cd exposure dose-dependently impaired proliferation of KGN granulosa cells and induced cell death. Ferroptosis was characterized by GPX4 depletion, TFRC/ACSL4 upregulation, oxidative stress, lipid peroxidation, and Fe²⁺ accumulation, which were mitigated by the Ferroptosis inhibitor ferrostatin-1. These findings suggest that environmental Cd exposure is associated with changes in levels of indicators of reduced ovarian reserve. Furthermore, Cd induces Ferroptosis in granulosa cells in vitro, suggesting a plausible mechanistic link, highlighting a potential target for reducing environmental reproductive toxicity.

Keywords

Cadmium exposure; Ferroptosis; Granulosa cells; Ovarian reserve; Reproductive treatment.

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