Hypoxia-induced apoptotic pathways and their contribution to fibrosis progression in wooden breast myopathy of fast-growing broilers
6 affiliations
- 1Yunnan Open University, Kunming, Yunnan, 650500, China.
- 2Yunnan Open University, Kunming, Yunnan, 650500, China. Electronic address: [email protected].
- 3State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai, 200240, China.
- 4College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang, Nanjing, Jiangsu, 210095, PR China.
- 5Department of Animal Science, University of Arkansas, Fayetteville, AR, 72701, USA.
- 6Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
Abstract
Fibrotic breast myopathy, including the Wooden Breast (WB) condition, represents one of the most economically and welfare-significant challenges confronting modern commercial broiler production. Despite growing recognition of the syndrome, the cellular and molecular mechanisms linking chronic myofibre hypoxia to the progressive fibrotic pathology remain incompletely defined. This study employed a four-group experimental model using 192 male Ross 308 broilers subjected to chronic hypobaric hypoxia (simulated altitude 3,000 m; 13.0% O₂) with and without pharmacological pan-caspase inhibition via Z-VAD-FMK (2 mg/kg, three times weekly) over a 42-day production period, to characterise the hypoxia–apoptosis–fibrosis axis in the pectoralis major muscle. Chronic hypoxia induced progressive HIF-1α protein accumulation (4.8-fold by Day 42; p < 0.001), accompanied by marked elevation in apoptotic index (14.3% TUNEL-positive nuclei; p < 0.001), a strongly pro-apoptotic Bax/Bcl-2 ratio shift (8.2 vs. 1.0 in controls), and downstream activation of the intrinsic caspase cascade (cleaved caspase-9, caspase-3, and PARP). Concomitantly, hypoxic birds demonstrated severe oxidative stress (4.4-fold MDA elevation; depleted SOD, CAT, GPx, and GSH), robust NF-κB-mediated inflammation (IL-1β, IL-6, IL-8, TNF-α all elevated > 8-fold), and extensive extracellular matrix remodelling (hydroxyproline content 7.8 µg/mg; fibrotic area 31.4%; upregulation of COL1A1, COL3A1, TGF-β1, MMP-2, and MMP-9). The blockade of pan-caspases markedly decreased the severity of WB lesions, fibrosis (19.8%), apoptosis (6.1%), pro-inflammatory cytokines, and ECM turnover without affecting the upstream accumulation of HIF-1α, indicating that the executioner caspase activation was one of the key nodes of signal amplification during the development of the disease. A highly significant positive correlation between the expressions of HIF-1α, apoptotic index, hydroxyproline level, and NF-κB (r = 0.78-0.87; all P < 0.001) provided evidence for a mechanistic involvement of hypoxia-induced apoptosis in the pathogenesis of the disorder.
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BibTeX
@article{yan2026hypoxiainduced,
title = {{Hypoxia-induced apoptotic pathways and their contribution to fibrosis progression in wooden breast myopathy of fast-growing broilers}},
author = {Shixiong Yan and Hongmei Shi and Muhammad Sarfaraz Iqbal and Gao Yang and Zhang Fei and Mikhlid H Almutairi},
journal = {Poultry Science},
year = {2026},
month = sep,
doi = {10.1016/j.psj.2026.107805},
url = {https://doi.org/10.1016/j.psj.2026.107805},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hypoxia-induced apoptotic pathways and their contribution to fibrosis progression in wooden breast myopathy of fast-growing broilers
AU - Shixiong Yan
AU - Hongmei Shi
AU - Muhammad Sarfaraz Iqbal
AU - Gao Yang
AU - Zhang Fei
AU - Mikhlid H Almutairi
PY - 2026
DA - 2026/09/21
JO - Poultry Science
DO - 10.1016/j.psj.2026.107805
UR - https://doi.org/10.1016/j.psj.2026.107805
AB - Fibrotic breast myopathy, including the Wooden Breast (WB) condition, represents one of the most economically and welfare-significant challenges confronting modern commercial broiler production. Despite growing recognition of the syndrome, the cellular and molecular mechanisms linking chronic myofibre hypoxia to the progressive fibrotic pathology remain incompletely defined. This study employed a four-group experimental model using 192 male Ross 308 broilers subjected to chronic hypobaric hypoxia (simulated altitude 3,000 m; 13.0% O₂) with and without pharmacological pan-caspase inhibition via Z-VAD-FMK (2 mg/kg, three times weekly) over a 42-day production period, to characterise the hypoxia–apoptosis–fibrosis axis in the pectoralis major muscle. Chronic hypoxia induced progressive HIF-1α protein accumulation (4.8-fold by Day 42; p < 0.001), accompanied by marked elevation in apoptotic index (14.3% TUNEL-positive nuclei; p < 0.001), a strongly pro-apoptotic Bax/Bcl-2 ratio shift (8.2 vs. 1.0 in controls), and downstream activation of the intrinsic caspase cascade (cleaved caspase-9, caspase-3, and PARP). Concomitantly, hypoxic birds demonstrated severe oxidative stress (4.4-fold MDA elevation; depleted SOD, CAT, GPx, and GSH), robust NF-κB-mediated inflammation (IL-1β, IL-6, IL-8, TNF-α all elevated > 8-fold), and extensive extracellular matrix remodelling (hydroxyproline content 7.8 µg/mg; fibrotic area 31.4%; upregulation of COL1A1, COL3A1, TGF-β1, MMP-2, and MMP-9). The blockade of pan-caspases markedly decreased the severity of WB lesions, fibrosis (19.8%), apoptosis (6.1%), pro-inflammatory cytokines, and ECM turnover without affecting the upstream accumulation of HIF-1α, indicating that the executioner caspase activation was one of the key nodes of signal amplification during the development of the disease. A highly significant positive correlation between the expressions of HIF-1α, apoptotic index, hydroxyproline level, and NF-κB (r = 0.78-0.87; all P < 0.001) provided evidence for a mechanistic involvement of hypoxia-induced apoptosis in the pathogenesis of the disorder.
SN - 0032-5791
SN - 1525-3171
ER -