Melatonin corrects HT-2 toxin-induced aberrant histone modifications and DNA hypermethylation in mouse oocytes

HT-2 toxin, a common grain contaminant, has been shown to impair mammalian reproductive function, but its specific effects on the epigenetic modifications of oocytes have not been systematically elucidated. This study aimed to investigate the impact of HT-2 toxin exposure on epigenetic modifications in mouse oocytes and the potential intervention of melatonin. The results revealed that HT-2 exposure downregulated the expression of histone methyltransferases (Suv39h2, Ehmt1, Ezh1, Ezh2) and the DNA demethylase Tet3, leading to reduced levels of repressive histone modifications (H3K9me3, H3K27me3) and abnormally elevated DNA methylation, which in turn compromised oocyte quality and significantly reduced the blastocyst formation rate after fertilization. The addition of melatonin effectively reversed the dysregulation of these epigenetics-related genes, restored histone modification and DNA methylation levels, and significantly improved embryonic developmental potential. This study reveals a novel mechanism by which melatonin mitigates reproductive toxicity through multi-target correction of HT-2-induced epigenetic errors, providing a potential strategy for preventing and addressing reproductive health issues caused by environmental toxins.