Acta Veterinaria et Zootechnica Sinica ›› 2025, Vol. 56 ›› Issue (12): 6477-6486.doi: 10.11843/j.issn.0366-6964.2025.12.048

• CLINICAL VETERINARY MEDICINE • Previous Articles     Next Articles

Proteomic Profiling Unveils the Protective Mechanism of Chlorogenic Acid against Zearalenone-induced Ovarian Granulosa Cell Death

YI Yanyan1, SUN Panpan2, SUN Na2, LI Hongquan2*   

  1. 1. The Youth Innovation Team of Shaanxi Universities, Yangling Vocational & Technical College, Yangling 712100, China;
    2. Shanxi Key Laboratory for Modernization of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China
  • Received:2025-03-31 Published:2025-12-24

Abstract: Zearalenone (ZEA) is a common mycotoxin that can cause severe reproductive toxicity. In our previous study, we found that chlorogenic acid could alleviate ZEA-induced ovarian granulosa cell toxicity, however, the mechanism of action is not clear. The aim of this study was to investigate the molecular mechanism by which chlorogenic acid antagonizes ZEA-induced follicular granulosa cell death in mice using proteomics techniques. Primary isolated and cultured mouse ovarian granulosa cells were divided into two groups: the ZEA group and the chlorogenic acid intervention group. After 24 h of treatment, the regulatory network of chlorogenic acid was systematically analyzed using quantitative proteomics technology combined with bioinformatics analysis and RT-qPCR validation. The results showed that a total of 32 differentially expressed proteins (DEPs) were identified in the chlorogenic acid-treated group compared with the ZEA-treated group, of which 15 were significantly up-regulated and 17 were significantly down-regulated. Through GO functional annotation and KEGG pathway enrichment analysis, the DEPs were mainly involved in biological processes such as mitotic regulation and cytoskeletal remodeling, and were significantly enriched in key regulatory pathways such as apoptosis, focal adhesion, Toll-like receptor signaling pathway and NF-κB signaling pathway. The changes in the expression of the key regulator RIPK1 were further verified by RT-qPCR and it was found that ZEA treatment significantly inhibited the expression of RIPK1, whereas chlorogenic acid intervention partially restored its expression level. Chlorogenic acid acts synergistically through multi-targets and multi-pathways such as regulation of cell cycle progression and apoptosis and maintenance of cellular structural homeostasis to antagonize ZEA-induced reproductive toxicity. In addition, RIPK1 may play a critical role as a key regulatory switch for cell survival and death. The present study reveals the mechanism of action of chlorogenic acid in antagonizing reproductive toxicity of ZEA at the protein level, providing new molecular targets and theoretical basis for the development of chlorogenic acid-based ZEA detoxifying agents or functional feed additives.

Key words: zearalenone, chlorogenic acid, ovarian granulosa cells, proteomics

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