Mitochondrial-targeted ROS scavenging by melatonin rescues 1-nitropyrene-induced defects in oocyte quality

As a prevalent and highly toxic environmental contaminant, 1‑nitropyrene (1‑NP) poses a significant threat to reproductive health, embryonic development, and genomic integrity. However, the specific mechanisms by which it impairs oocyte quality remain incompletely understood. Melatonin, a potent free‑radical scavenger, has been shown to protect the reproductive system from oxidative damage. In this study, we investigated the deleterious effects of 1‑NP on mouse oocytes and evaluated the potential of melatonin to counteract such toxicity. Our results demonstrate that 1‑NP exposure severely compromises oocyte maturation, fertilization, and subsequent preimplantation development. Transcriptomic sequencing revealed that 1‑NP dramatically alters the oocyte gene expression profile, leading to defective clearance of maternally inherited mitochondrial transcripts. This disruption subsequently induces mitochondrial dysfunction and oxidative stress. In parallel, 1‑NP treatment also perturbed key epigenetic modifications. In contrast, melatonin co‑treatment effectively ameliorated 1‑NP‑induced meiotic spindle anomalies, chromosomal aneuploidy, mitochondrial dysfunction, oxidative stress, and epigenetic aberrations, thereby restoring oocyte quality and post‑fertilization developmental competence. Notably, melatonin reversed the majority of the aberrant gene expression patterns elicited by 1‑NP. Strikingly, treatment with the mitochondria‑targeted antioxidant Mito‑TEMPO alone in the 1‑NP exposure system significantly improved oocyte maturation rates, restored mitochondrial membrane potential, and reduced ROS levels. Together, these findings indicate that melatonin protects mouse oocytes from 1‑NP‑induced damage primarily by targeting mitochondria and clearing mitochondrial ROS, thereby alleviating oxidative stress and revealing a promising therapeutic strategy against environmental reproductive toxicants.