(P30-035-25) Role of SELENOS in the Development of Nutritional Muscular Dystrophy in Se Deficient Chickens Under Heat Stress

Objectives: Dietary Se deficiency induces nutritional muscular dystrophy (NMD) in the skeletal muscle of broiler chickens under heat stress. This study was to determine the role and mechanism of SELENOS in this pathogenesis.

Methods: One-day-old male Cobb broilers (n = 6 cages/diet, 6 broilers/cage) were fed a Se-deficient diet (Se-Def, 47 μg Se/kg) or the diet supplemented with 0.3 mg Se/kg as Na₂SeO₃ (Se-adeq) for 6 weeks under heat stress. In vitro, SELENOS was knocked down in the C2C12 cell line, and the cells were cultured in differentiation medium under continuous heat stress conditions for 6 days to form multinucleated myotubes.

Results: Compared with Se-adeq., Se-Def induced NMD in the pectoral muscle, accompanied by endoplasmic reticulum (ER) stress, evidenced by reduced muscle size, severe muscle fiber atrophy, and swollen, dilated ER with blurred lumen edges. Additionally, Se-Def aggravated the stress response and induced immune dysfunction, characterized by increased serum cortisol, IgA, IgG, IgM, and lipopolysaccharides (LPS) levels, along with decreased T4 and IL-1β levels. Meat quality was also compromised by Se-Def, as shown with a reduction in muscle pH and an increase in lightness (L*). Mechanistically, Se deficiency triggered ER stress with upregulation of GRP78, PERK, and CHOP and downregulation of phosphorylated eIF2α. This was followed by apoptosis, characterized by the upregulation of Bax and caspase-9 and downregulation of Bcl-2. These responses were accompanied by downregulation of selenoproteins, particularly SELENOW and SELENOS. Consistently, SELENOS knockdown in C2C12 cells and differentiated myotubes aggravated ER stress-induced apoptosis and impaired myotube differentiation under the heat stress condition.

Conclusions: Our results suggest a potential role of SELENOS in regulating ER stress and apoptosis associated with the pathogenesis of Se deficiency-induced NMD in chickens under heat stress.

Funding Sources: No external funding