Resveratrol Mitigates Haloacetaldehyde Disinfection By-Products (HAL-DBPs)-Induced Oocyte Developmental Toxicity via Mitochondria-Dependent Pathways.

Haloacetaldehyde disinfection by-products (HAL-DBPs), a class of unregulated emerging contaminants formed during drinking water chlorination, are widely detected in the aquatic environment, yet their potential reproductive toxicity remains poorly understood. In this study, we used a chronic drinking water exposure model in mice (90 days) and subsequently evaluated oocyte developmental competence in vitro. A chronic drinking water exposure model with environmentally relevant concentrations of HAL-DBPs was established to systematically evaluate their effects on oocyte developmental competence and to investigate the protective role of the natural antioxidant resveratrol (RES). The results showed that HAL-DBPs exposure significantly reduced oocyte maturation rate and early embryonic development potential, leading to spindle disorganization, chromosomal misalignment, and disruption of the actin cytoskeleton. Moreover, HAL-DBPs induced mitochondrial membrane potential loss, lipid metabolic disorder, impaired autophagy-lysosomal flux, excessive ROS accumulation, DNA damage, and apoptosis. Notably, RES cotreatment markedly alleviated these adverse effects by restoring mitochondrial function and redox homeostasis, reducing DNA damage and apoptosis, and preserving cytoskeletal integrity. Collectively, this study provides the first evidence that HAL-DBPs directly impair female germ cells through mitochondria-dependent oxidative stress mechanisms and proposes RES as a promising natural antioxidant intervention to mitigate reproductive toxicity associated with drinking water disinfection by-products.