EGCG protects mouse oocytes from malathion-induced damage by preserving mitochondrial function, genomic integrity,...

Organophosphate pesticides such as malathion (Mal) pose a significant threat to female reproductive health, primarily by impairing oocyte quality, yet effective protective countermeasures remain limited. This study investigated whether epigallocatechin gallate (EGCG), a green tea polyphenol with known antioxidant properties, could protect oocytes by targeting mitochondrial function, a key mechanism implicated in its toxicity. Using a mouse in vitro oocyte maturation model, we demonstrate that Mal exposure severely disrupts both nuclear maturation, indicated by suppressed polar body extrusion, and cytoplasmic maturation. The toxicity manifests through a defined mitochondrion-centric pathological cascade: Mal induces the loss of mitochondrial membrane potential (ΔΨm), which in turn triggers excessive reactive oxygen species (ROS) production and activates early apoptosis. At the transcriptional level, Mal induced the disordered mitochondrial biogenesis, impaired Nrf2-mediated antioxidant signaling and activated apoptotic pathways. These subcellular injuries lead to profound functional and structural defects, including DNA damage accumulation (γ-H2AX foci), meiotic spindle disruption, chromosome misalignment, and loss of Juno protein on the oocyte surface, ultimately resulting in a significantly reduced sperm-binding capacity. Importantly, co-treatment with EGCG effectively mitigated this entire cascade. EGCG preserved ΔΨm, suppressed oxidative stress and apoptosis, by normalizing these transcriptional alterations to improve mitochondrial biogenesis, antioxidant capacity and anti-apoptotic status. EGCG restored Juno expression, reduced DNA damage, maintained spindle integrity, and improved fertilization competence. Our findings demonstrate that EGCG rescues Mal-induced oocyte damage primarily by preserving mitochondrial integrity, Nrf2-dependent antioxidant defense and apoptotic signaling, thereby safeguarding both cytoplasmic maturation and nuclear genomic stability. This highlights its potential as a mitochondrion-targeting nutraceutical strategy to counteract reproductive toxicity from environmental pesticides.