Melatonin partially rescues defects induced by tranexamic acid exposure during oocyte maturation in mice.

Tranexamic acid (TXA) is widely used among young women because of its ability to whiten skin and treat menorrhagia. Nevertheless, its potential effects on oocyte maturation and quality have not yet been clearly clarified. Melatonin (MT) is an endogenous hormone released by the pineal gland and believed to protect cells from oxidative stress injury. In the present study, we used an in vitro maturation model to investigate the toxicity of TXA and the protective role of MT in mouse oocytes. Compared with the control group, the TXA-exposed group had significantly lower nuclear maturation (57.72% vs. 94.08%, < 0.001) and early embryo cleavage rates (38.18% vs. 87.66%, < 0.001). Further study showed that spindle organization (52.56% vs. 18.77%, < 0.01) and chromosome alignment (33.23% vs. 16.66%, < 0.01) were also disrupted after TXA treatment. Mechanistically, we have demonstrated that TXA induced early apoptosis of oocytes ( < 0.001) by raising the level of reactive oxygen species ( < 0.001), which was consistent with an increase in mitochondrial damage ( < 0.01). Fortunately, all these effects except the spindle defect were successfully rescued by an appropriate level of MT. Collectively, our findings indicate that MT could partially reverse TXA-induced oocyte quality deterioration in mice by effectively improving mitochondrial function and reducing oxidative stress-mediated apoptosis. Tranexamic acid is increasingly used to whiten skin, reverse dermal damages, and treat heavy menstrual bleeding in young women. However, its potential toxicity in mammalian oocytes is still unclear. Our study revealed that tranexamic acid exposure impaired the mouse oocyte quality and subsequent embryo development. Meanwhile, melatonin has been found to exert beneficial effects in reducing tranexamic acid-induced mitochondrial dysfunction and oxidative stress.