Oxidative Stress and Endoplasmic Reticulum Stress Are Involved in the Protective Effect of Alpha Lipoic Acid Against Heat Damage in Chicken Testes

SIMPLE SUMMARY: In male animals, heat stress causes injury to the testes, resulting in an increase in the number of deformed sperm, a reduction in testosterone production, and consequently, reduced reproductive performance. As an important antioxidant, alpha lipoic acid (ALA) has been reported to have a protective effect against testicular injury caused by various pathological factors. However, few studies have focused on the role of ALA in heat-induced testicular lesions. In this study, the effects of ALA on histopathological parameters, the activity of key antioxidant enzymes involved in oxidative stress, biomarkers of endoplasmic reticulum stress signaling in the testicular tissue, and testosterone levels in serum were evaluated in heat-stressed chickens. The results showed that ALA significantly alleviated heat stress-induced adverse effects by affecting the activities of antioxidant enzymes, the expression of endoplasmic reticulum stress-related apoptotic modulators, and the protein levels of steroidogenic genes in the testes of chickens exposed to heat stress. These results suggest that in chickens, ALA may be beneficial for ameliorating decreased reproductive performance caused by heat stress and this study provides the basis for the design of novel therapies for heat-induced testicular damage. ABSTRACT: Heat stress (HS) causes testicular injury, resulting in decreased fertility. Alpha-lipoic acid (ALA) is a well-known antioxidant. The aim of this study was to investigate the protective effects of ALA on HS-induced testicular damage in chickens. Histological changes; biomarkers of oxidative stress, including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA); markers of endoplasmic reticulum (ER) stress, including glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP); apoptosis-related modulators, including Bax, Bcl-2, and caspase 3, in testicular tissue and serum testosterone levels were evaluated in chickens under heat stress. Heat stress induces spermatogenic cell abnormalities in chicken testes. Compared to the HS group, the histomorphological abnormalities in testicular tissue were visibly ameliorated, with significant increases in the enzyme activities of GPx, SOD, and CAT, increased serum testosterone concentration, and decreased MDA levels in the ALA + HS group. Consistent with these results, compared with the HS group, the protein levels of GRP78, CHOP, caspase 3, and Bax were significantly decreased, whereas Bcl-2, StAR, and 3β-HSD protein levels were increased in the ALA + HS group. Collectively, these findings suggest that ALA significantly ameliorates the heat-induced histomorphological abnormalities in the testes and decreased testosterone production by potentiating the activities of anti-oxidative enzymes (GPx, SOD, and CAT), inhibiting ER stress-related apoptotic pathways (Bax, Bcl-2, and caspase 3), and increasing steroidogenic gene (StAR and 3β-HSD) expression in chickens.