Melatonin improves oxybenzone-exposed oocyte quality during meiotic maturation by promoting mitochondrial homeostasis and function

Oxybenzone (OBZ), an endocrine-disrupting chemical (EDC) frequently used in sunscreens and cosmetics, has been found to cause mitochondrial toxicity, which may impede the development of the female reproductive system. Melatonin (MT), a free radical scavenger produced by the pineal gland, can counteract oxidative damage caused by EDCs during oocyte maturation and support the regulation of mitochondrial dynamics. However, the precise mechanisms by which MT modulates mitochondrial homeostasis in oocytes and alleviates the harmful effects of OBZ exposure remain elusive. Here, we evaluated the effects of MT in OBZ exposed oocytes by assessing parameters such as mitochondrial dynamics, calcium levels, mitochondrial distribution and membrane potential, gene expression related to the mitochondrial electron transport chain (ETC), reactive oxygen species (ROS) production, antioxidant enzyme activity, and typical spindle configuration. In OBZ-exposed mice, MT supplementation both in vitro and in vivo effectively increased the transcription and translation of the mitochondrial fusion genes Mfn1/2 and Opa1, while reducing the transcription and translation of the mitochondrial fission genes Drp1, Fis1 and Mff, as well as reducing cytosolic and mitochondrial calcium levels. Additionally, OBZ causes significant mitochondrial defects, including abnormal mitochondrial distribution, disrupted spindle assembly, decreased in membrane potential, reduced expression of ETC-related genes, elevated ROS levels, reduced glutathione (GSH) content, and suppressed antioxidant enzyme activity, all of which can be restored through MT treatment. By microtranscriptomic analysis, we further discovered that MT-induced oocyte quality recovery may be mediated by enhancing calcium signaling pathway and ATP-dependent chromatin remodeling in OBZ-exposed mice. In conclusion, our findings suggest that MT administration, both in vivo and in vitro, mitigates OBZ-induced oocyte defects by preserving mitochondrial homeostasis, mitigating calcium overload, and reducing oxidative stress, offering valuable insights into potential treatments for infertility related to poor mitochondrial quality in oocytes.