Melatonin improves the quality of rotenone-exposed mouse oocytes through association with histone modifications

Rotenone, an insecticide that inhibits mitochondrial complex I and generates oxidative stress, is responsible for neurological disorders and affects the female reproductive system. However, the underlying mechanism is not fully understood. Melatonin, a potential free-radical scavenger, has been shown to protect the reproductive system from oxidative damage. In this study, we investigated the impact of rotenone on mouse oocyte quality and evaluated the protective effect of melatonin on oocytes exposed to rotenone. Our results showed that rotenone impaired mouse oocyte maturation and early embryo cleavage. However, melatonin prevented these negative effects by ameliorating rotenone-induced mitochondrial dysfunction and dynamic imbalance, intracellular Ca²⁺ homeostasis damage, ER stress, early apoptosis, meiotic spindle formation disruption, and aneuploidy in oocytes. Additionally, RNA sequencing analysis showed that rotenone exposure changed the expression of multiple genes involved in histone methylation and acetylation modifications that result in mouse meiotic defects. However, melatonin partially rescued these defects. These findings suggest that melatonin has protective effects against rotenone-induced mouse oocyte defects.