Melatonin enhances reproductive capability in HT-2 toxin-treated oocytes via mitochondrial restoration

HT-2 toxin, a type A trichothecene mycotoxin produced by fungi such as Fusarium, is widely present in nature in moldy crops and adversely affects mammalian reproduction. Melatonin, a natural antioxidant, exhibits protective effects on cells. This study investigated the impact of HT-2 toxin on mouse oocytes cultured in vitro and evaluated the rescuing effect of melatonin on oocytes exposed to HT-2 toxin. Our results demonstrate that HT-2 toxin severely disrupted oocyte maturation, manifested by the failure of the first polar body extrusion in the majority of oocytes concomitant with impaired mitochondrial function and elevated reactive oxygen species (ROS) levels. Nevertheless, melatonin supplementation partially rescued the HT-2-induced impairment of mouse oocyte maturation. RNA-seq analysis revealed that HT-2 exposure altered the expression of 1827 genes in mature mouse oocytes, many of which are associated with oxidative stress, mitochondrial function, and energy supply. The addition of melatonin reduced abnormalities in spindle assembly, accumulation of ROS, DNA damage, and apoptosis in mouse oocytes exposed to HT-2 toxin. Importantly, melatonin upregulated the expression of genes related to mitochondrial function, thereby enhancing mitochondrial function in HT-2-exposed mouse oocytes. This further mitigated DNA damage and apoptosis caused by oxidative stress. In conclusion, our results indicate that melatonin exerts protective effects against the decline in oocyte quality induced by HT-2 toxin in mice.