Spermidine alleviates 2,2-dichloroacetamide/ 2,2-dibromoacetamide-exposed mouse oocyte toxicity by restoring...

Environmental toxicants pose a major threat to human health, yet the reproductive toxicity of haloacetamide disinfection byproducts remains largely unclear. Here, we examined the effects of two haloacetamides, 2,2-dichloroacetamide (DCAcAm) and 2,2-dibromoacetamide (DBAcAm), on mouse oocyte maturation and identified the underlying mechanisms of toxicity. Both compounds markedly impaired meiotic spindle assembly and compromised the function of multiple organelles, including mitochondria, the endoplasmic reticulum, and the Golgi apparatus, primarily through autophagy dysregulation at specific exposure concentrations, as evidenced by the observation that more than half of the oocytes failed to progress beyond the MII stage. Spermidine supplementation effectively restored autophagic activity and rescued the associated cellular defects, thereby improving both nuclear and cytoplasmic maturation in oocytes. Collectively, these findings demonstrate that spermidine alleviates toxicant-induced deterioration of oocyte quality by regulating autophagy and highlight its potential therapeutic value for reproductive protection and clinical application.