Melatonin protects porcine oocytes from gossypol-induced meiosis defects via regulation of SIRT1-mediated mitophagy.

Abstract

Cottonseed meal (CSM) is an ideal source of protein feed ingredients. However, the gossypol contained in it has toxic effects on animals, limiting its use in livestock production. The underlying mechanisms remain largely unknown. This study aimed to investigate the adverse effects of gossypol exposure and assess whether melatonin, a natural antioxidant, could alleviate oocyte damage induced by gossypol. Porcine cumulus oocyte complexes (COCs) were treated with gossypol alone or co-treated with melatonin for 44 h during in vitro maturation. The results demonstrated that gossypol exposure induced oxidative stress and mitochondrial dysfunction, leading to oocyte maturation failure. Conversely, melatonin co-treatment mitigated these detrimental effects, by promoting oocyte mitophagy, as evidenced by the upregulation of PINK1, Parkin, and LC3 expressions, along with the downregulation of P62. Further investigation revealed that gossypol treatment significantly decreased SIRT1 protein expression, while melatonin co-treatment markedly increased it. Using the SIRT1 inhibitor Ex527 confirmed that melatonin enhances mitophagy through SIRT1, improving mitochondrial function and rescuing oocyte maturation. This study revealed the potential harm of gossypol on mammalian reproductive health, provided experimental reference for the protective effect of melatonin, and provided theoretical basis for the effective prevention and treatment of reproductive damage caused by gossypol.