SELENOS Is Associated with Endoplasmic Reticulum Stress Activation in Selenium Deficiency-Induced Nutritional Muscular Dystrophy in Chicks Exposed to Heat Stress.

BACKGROUND

Broiler chickens are fast-growing and highly susceptible to dietary selenium (Se) deficiency, with environmental stressors like heat stress further intensifying their vulnerability.

OBJECTIVES

Here, we investigated the mechanisms underlying Se deficiency-induced nutritional muscular dystrophy (NMD) in broilers under heat stress.

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 a Se-Def diet supplemented with 0.3 mg Se/kg Na2SeO3 for 6 wk.

RESULTS

Compared with the control, Se-Def induced NMD in the pectoral muscle, accompanied by endoplasmic reticulum (ER) stress, as indicated by reduced muscle size, severe fiber atrophy, and swollen ER with blurred lumen edges. Additionally, serum analysis revealed that Se-Def aggravated stress responses and immune dysfunction, with elevated cortisol, immunoglobulins (IgA, IgG, IgM), and lipopolysaccharide levels, and decreased T4 and interleukins-1β. Meat quality was also impaired, with lower pH and higher lightness (L∗). Mechanistically, Se deficiency was associated with increased markers of ER stress, shown by increased glucose-regulated protein 78, protein kinase RNA-like endoplasmic reticulum kinase, and C/EBP homologous protein, along with changes consistent with apoptosis with upregulated Bax and Caspase-9 and downregulated Bcl-2. These changes coincided with reduced selenoproteins, notably SELENOW and SELENOS. Consistently, SELENOS knockdown in C2C12 cells and myotubes exacerbated ER stress-induced apoptosis and impaired differentiation under heat stress.

CONCLUSIONS

In conclusion, our findings support a contributory role for SELENOS in ER stress-related responses and apoptosis-associated signaling, providing insights into Se deficiency-induced NMD and suggesting SELENOS as a potential therapeutic target for muscle disorders under stress conditions.