Ellagic acid mitigates follicular atresia in laying chickens via GPX4 upregulation to block ferroptosis and p53 suppression to attenuate DNA damage
- 1Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
- 2Corresponding author.
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.
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BibTeX
@article{yuan2026ellagic,
title = {{Ellagic acid mitigates follicular atresia in laying chickens via GPX4 upregulation to block ferroptosis and p53 suppression to attenuate DNA damage}},
author = {Qiongyu Yuan and Xiaojuan Tang and Zhaoyu Yang and Yingyu Xiao and Jing Dong and Xiangyu Cai and Wanyue Gao and Yue Wang and Weidong Zeng and Caiqiao Zhang and Yuling Mi},
journal = {Redox Biology},
year = {2026},
month = oct,
doi = {10.1016/j.redox.2026.104444},
url = {https://doi.org/10.1016/j.redox.2026.104444},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Ellagic acid mitigates follicular atresia in laying chickens via GPX4 upregulation to block ferroptosis and p53 suppression to attenuate DNA damage
AU - Qiongyu Yuan
AU - Xiaojuan Tang
AU - Zhaoyu Yang
AU - Yingyu Xiao
AU - Jing Dong
AU - Xiangyu Cai
AU - Wanyue Gao
AU - Yue Wang
AU - Weidong Zeng
AU - Caiqiao Zhang
AU - Yuling Mi
PY - 2026
DA - 2026/10/19
JO - Redox Biology
DO - 10.1016/j.redox.2026.104444
UR - https://doi.org/10.1016/j.redox.2026.104444
AB - 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.
SN - 2213-2317
ER -