Melatonin safeguards embryo and blastoid development against oxybenzone toxicity via a mitochondrial-linked NAD+ and glucose metabolic axis.

Oxybenzone (OBZ), a widely used ultraviolet filter detected in human bodily fluids, has been associated with reproductive toxicity, yet its effects on preimplantation development remain unclear. Using mouse embryos, human tripronuclear embryos, and blastoids, we investigated whether melatonin (MT) could mitigate OBZ-induced developmental defects. OBZ exposure impaired blastocyst formation, disrupted redox homeostasis, increased oxidative stress, and reduced developmental potential. MT supplementation restored glucose metabolism, elevated NAD+ levels, re-established redox balance, and enhanced histone acetylation, thereby preserving pluripotency and normal gene expression. This integrated metabolic-redox-epigenetic axis underlies the protective effects of MT and also improved embryo quality and reproductive outcomes in vivo. Our findings reveal a previously unrecognized mechanism by which MT safeguards early embryonic development through coordinated regulation of energy metabolism, oxidative status, and chromatin modification, providing new mechanistic insight for improving assisted reproduction.