Aflatoxin B1 triggers ferroptosis via inhibiting the NRF2 signaling pathway in duck granulosa cells

  • Poult Sci. 2025 Dec;104(12):105993. doi: 10.1016/j.psj.2025.105993.
Yaru Chen  1 ,  Lei Wang  2 ,  Ming Fu  1 ,  Tao Huang  1 ,  Hao Zhang  1 ,  Jie Shen  1 ,  Ailuan Pan  1 ,  Zhenhua Liang  1 ,  Jing Sun  1 ,  Jinping Du  1 ,  Jinsong Pi  1 ,  Yan Wu  3
Affiliations
  • 1. Institute of Animal Science and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430064, China; Hubei Key Laboratory of Animal Embryo Engineering and Molecular Breeding, Wuhan 430064, China.
  • 2. Wuhan Green Giant Agriculture & Animal Husbandry Company Limited, Wuhan 432200, China.
  • 3. Institute of Animal Science and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430064, China; Hubei Key Laboratory of Animal Embryo Engineering and Molecular Breeding, Wuhan 430064, China. Electronic address: [email protected].
PMID: 41197355 DOI: 10.1016/j.psj.2025.105993
Abstract

Aflatoxin B1 (AFB1) is an unavoidable food and environmental contaminant that exerts toxicity on female reproductive system, poses major threats to livestock and poultry breeding. However, the underlying mechanisms of AFB1-induced reproductive toxicity and effective interventions remain unclear. We observed that AFB1 exposure significantly suppressed granulosa cell growth and cell viability in ducks. Further analysis revealed that AFB1 exposure triggered excessive oxidative stress in duck granulosa cells. Additionally, AFB1 exposure induced lipid peroxidation, mitochondrial dysfunction and Ferroptosis, which were alleviated by Ferrostatin-1. Transcriptomic analysis revealed the suppression of the NRF2 signaling pathway in AFB1 exposure. Meanwhile, NRF2 inhibitor (ML385) abolished the protective effect of Ferrostatin-1 and exacerbated Ferroptosis, suggesting that NRF2 plays a protective role against AFB1-induced cytotoxicity. Moreover, seleniummethionine (Se-Met), an NRF2 pathway activator, effectively alleviated AFB1-induced granulosa cell damage. This study elucidates the protective mechanism of the NRF2 signaling pathway against AFB1-induced Ferroptosis and highlights the potential of Se-Met as a therapeutic strategy for alleviating AFB1-induced reproductive dysfunction in poultry.

Keywords
AFB1; Ferroptosis; Granulosa cell; NRF2; Selenomethionine.
Products