Potential role of endoplasmic reticulum stress in broiler woody breast myopathy.

Although broiler (meat-type) chickens are one of the most efficient protein sources that supports the livelihoods and food security of billions of people worldwide, they are facing several challenges. Due to its unknown etiology and heavy economic impact, woody breast (WB) myopathy is one of the most challenging problems facing the poultry industry, and for which there is no effective solution. Here, using a primary chicken myotube culture model, we show that hypoxia and endoplasmic reticulum (ER) stress are an integral component of the etiology of the myopathy. Multiple components of the ER stress response are significantly upregulated in WB as compared with normal muscle, and this response was mimicked by hypoxic conditions in chicken primary myotube culture. In addition, apoptotic pathways were activated as indicated by increases in active caspase 3 protein levels in both WB-affected tissues and hypoxic myotube culture, and caspase 3 activity and apoptosis in hypoxic myotube culture. Finally, as a phenotypic hallmark of WB is enhanced fibrosis and increased collagen aggregation, here, we show that hypoxic conditions increase collagen 1A1 and 1A2 gene expression, as well as collagen 1 protein levels in primary myotubes. These effects were partially reversed by tauroursodeoxycholic acid (TUDCA), an ER-stress inhibitor, in myotube culture. Taken together, these findings indicate that hypoxia and ER stress are present in WB, hypoxia can upregulate the cell death arm of the unfolded protein response (UPR) and lead to collagen production in a culture model of WB. This opens new vistas for potential mechanistic targets for future effective interventions to mitigate this myopathy.