Melatonin restores the declining maturation quality and early embryonic development of oocytes in aged mice

With increase in women's age, the reproductive capability of female mammals decreases dramatically caused by age-related oxidative stress, coinciding with the decline in the ovarian reserve, and the quality and quantity of oocytes, which is the main determinant of female fertility. Melatonin, as an effective antioxidant and antiaging substance, is secreted by the pineal gland and been found in the follicular fluid as well, which has been turned out to enable to protect oocytes from oxidative stress during ovulation. However, the beneficial effects of melatonin on meiotic maturation in vitro and early embryo development of aged oocytes are still not fully understood. Thus, the aim of this study is to explore the potential mechanism of melatonin to improve the oocytes maturation and early embryonic development. The results suggested that oocyte quality decreased with age, whereas 10^-6 M melatonin supplementation can significantly prompt the maturation quality of oocytes, the rate of fertilization and the formation rate of blastocyst. Mechanistic investigation indicated that melatonin supplementation not only restored the function of mitochondria by reducing reactive oxygen species (ROS) generation and early apoptosis, but also increased the level of ATP and total GSH through enhancing the mRNA expression levels of SIRT1, SIRT3, GPX4, SOD1 and SOD2. In conclusion, melatonin could alleviate the impairment of age-related oxidative stress to meiotic maturation and early embryonic development of oocytes. This study may provide a potential remediation strategy to improve the quality of oocytes from aged women and the efficiency of assisted reproductive technologies.