Melatonin ameliorates oxybenzone-induced meiotic defects in mouse oocytes via regulation of mitochondrial dynamics and calcium signaling.

Oxybenzone (2-Hydroxy-4-methoxybenzophenone, OBZ) is an organic ultraviolet filter extensively used in sunscreens and cosmetics, and has become a pervasive contaminant in aquatic environments. While its endocrine-disrupting properties and adverse reproductive effects are recognized, potential impacts on oocyte mitochondrial physiology remain incompletely understood. In this study, we investigated whether melatonin (MT), a pineal-derived antioxidant that regulates mitochondrial dynamics, can counteract OBZ-induced oocyte damage. Key indicators were evaluated in both in vivo and in vitro models, including mitochondrial dynamics, Ca²⁺ homeostasis, distribution and membrane potential (ΔΨm), electron transport chain (ETC) gene expression, reactive oxygen species (ROS) generation, antioxidant enzyme activity, and spindle organization. MT supplementation restored mitochondrial homeostasis by promoting fusion gene expression (Mfn1/2, Opa1) and suppressing fission genes (Drp1, Fis1, Mff), while reducing OBZ-induced cytosolic and mitochondrial Ca²⁺ overload. These protective effects reversed OBZ-related abnormalities such as disrupted mitochondrial distribution, spindle disorganization, decreased ΔΨm, downregulated ETC genes, and pronounced oxidative stress characterized by elevated ROS and diminished GSH. Microtranscriptomic analysis further suggested involvement of enhanced Ca²⁺ signaling and ATP-dependent chromatin remodeling in MT-mediated oocyte protection. Overall, our findings indicate that mitochondrial dysfunction is a critical component of OBZ-induced oocyte impairment, and support MT as a potential intervention to preserve oocyte quality under environmental toxicant exposure.