Melatonin mitigates polystyrene nanoplastics-induced impairment of oocyte maturation in mice

The widespread contamination of polystyrene nanoparticles (PS-NPs) has emerged as a significant global concern due to its potential threats to human and animal health. Although the toxicity of PS-NPs to ovarian function has been established, how to relieve the damage of PS-NPs to oocyte maturation remains elusive. Since melatonin (MLT) plays an essential role in regulating ovarian function. This study is the first attempt to explore the protective roles of melatonin in counteracting the maturation defects of oocytes caused by PS-NPs exposure. In this investigation, the reproductive toxicity of PS-NPs was evaluated after continued exposure for 35 days. After exposure, cumulus oocyte complexes (COCs) obtained from PS-NPs exposed-mice were cultured in vitro, meanwhile the various concentration MLT were supplemented into the culture medium to determine the beneficial roles. The results revealed that PS-NPs exposure could impede the meiotic progression, fertilization competence and subsequent embryonic development of oocytes. These impairments are likely mediated through multiple mechanisms, including excessive ROS generation, reduced ATP contents, mitochondrial dysfunction and subsequent induction of early apoptosis. Besides, PS-NPs exposure was found to compromise the architecture of spindle and the alignment of chromosome via altering the key epigenetic markers (tubulin-ace and H4K12ac). Notably, these adverse effects could be alleviated after MLT administration. Further analysis demonstrated that MLT supplementation significantly enhanced antioxidant capacity and mitochondrial dynamics, which indicated by enlarged the mRNA expression levels of anti-oxidative enzyme and mitochondrial dynamics-related genes. In conclusion, MLT could rescue PS-NPs-induced oocyte quality decline by ameliorating oxidative stress, restoring mitochondrial function, and normalizing epigenetic modifications.