Melatonin regulates the activities of ovary and delays the fertility decline in female animals via MT1/AMPK pathway

mol/L)-treated group than that in the controls. When these blastocysts were transferred to recipients, the litter size was also significantly larger in melatonin treated mice than that in controls. The increases in TAOC and SOD level and decreases in MDA were detected in ovaries and uterus from melatonin-treated mice compared to the controls. Melatonin reduced ROS level and maintained mitochondrial membrane potential in the oocytes cultured in vitro. Mechanistically studies revealed that the beneficial effects of melatonin on oocytes were mediated by MT1 receptor and AMPK pathway. Thereafter, MT1 knocking out (MT1-KO) were generated and shown significantly reduced number of oocytes and litter size. The expression of SIRT1, C-myc, and CHOP were downregulated in the ovary of MT1-KO mice, but SIRT1 and p-NF-kB protein level were elevated in response to disturbed redox balance. The results have convincingly proven that melatonin administration delays ovary aging and improves fertility in mice via MT1/AMPK pathway.