{
  "abstract": "Follicular atresia is a critical factor limiting the reproductive lifespan of laying chickens, a process primarily driven by the progressive death of granulosa cells. This study investigates the precise redox mechanisms underlying chicken follicular atresia and evaluates the cytoprotective efficacy of Ellagic Acid (EA). In vivo and in vitro analyses revealed that this atretic process is executed by a lethal synergy between lipid peroxidation-driven ferroptosis (characterized by mitochondrial collapse and glutathione peroxidase 4 (GPX4) depletion) and DNA damage response-triggered apoptosis (characterized by the activation of the p53 signaling axis). EA intervention successfully mitigated this structural and cellular degeneration. Mechanistically, molecular dynamics simulations and cellular thermal shift assays provided compelling biophysical evidence that EA physically binds and structurally stabilizes the active pockets of both GPX4 and p53. The indispensability of this dual-targeting paradigm was validated through siRNA-mediated gene silencing: GPX4 knockdown abrogated EA's ability to restore intracellular glutathione and suppress ferroptosis, while p53 knockdown blunted its anti-apoptotic rescue effects. A double knockdown neutralized EA's protective pleiotropy. In conclusion, chicken follicular atresia is structurally governed by a GPX4/p53-mediated interplay between ferroptosis and apoptosis. EA functions beyond a generic antioxidant as a specific, dual-target pharmacological agent, highlighting targeted redox interventions as a highly viable strategy for preserving the ovarian reserve in laying chickens.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China",
    "Corresponding author."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qiongyu Yuan"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaojuan Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhaoyu Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yingyu Xiao"
    },
    {
      "affs": [
        0
      ],
      "name": "Jing Dong"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangyu Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "Wanyue Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yue Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Weidong Zeng"
    },
    {
      "affs": [
        1
      ],
      "name": "Caiqiao Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuling Mi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/37b8e91zmw6cv.bib",
  "cited_by": 0,
  "doi": "10.1016/j.redox.2026.104444",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S221323172600443X",
  "id": "37b8e91zmw6cv",
  "issns": [
    "2213-2317"
  ],
  "landing_url": "https://doi.org/10.1016/j.redox.2026.104444",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Paper"
    ],
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "lcc",
      "R5-920"
    ],
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7222971715",
  "pdf_url": null,
  "pmcid": "PMC13720375",
  "pmid": "42925725",
  "published": "2026-10-19",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/37b8e91zmw6cv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:44:53Z",
      "native_id": "358a3819a1dd488aa08ffcb77cb8bd60",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.redox.2026.104444"
    },
    {
      "first_seen": "2026-11-03T12:21:16Z",
      "native_id": "PMC13720375",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.redox.2026.104444"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|Redox biology and oxidative stress",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "lcc:QH301-705.5",
      "subfield": "general"
    },
    {
      "field": "medicine",
      "origin": "lcc:R5-920",
      "subfield": "general"
    }
  ],
  "title": "Ellagic acid mitigates follicular atresia in laying chickens via GPX4 upregulation to block ferroptosis and p53 suppression to attenuate DNA damage",
  "title_text": "Ellagic acid mitigates follicular atresia in laying chickens via GPX4 upregulation to block ferroptosis and p53 suppression to attenuate DNA damage",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:16Z",
  "url": "https://research.draconitic.com/paper/37b8e91zmw6cv",
  "venue": "Redox Biology",
  "versions": []
}