Long‐term melatonin treatment delays ovarian aging

Ovarian aging is characterized by gradual declines in oocyte quantity and quality. Melatonin is considered an anti‐aging agent due to its cytoprotective actions as an antioxidant. This study examined whether long‐term melatonin treatment would delay ovarian aging in mice. Female ICR mice (10 weeks old) were given melatonin‐containing water (100 μg/mL; melatonin) or water only until 43 weeks of age. Their oocytes were recovered from the oviduct, and in vitro fertilization was performed. The ovaries were used for a histological analysis of the number of follicles. The mRNA expression of the aging‐related sirtuin genes (SIRT1, SIRT3) and the autophagy‐related gene (LC3) and the telomere length of the ovarian chromosomes were analyzed. Transcriptome changes in the ovaries were also characterized using microarray. The number of ovulated oocytes decreased with age; however, it was greater in melatonin‐treated mice than that from control animals. The decreased fertilization rate and blastocyst rate during aging also were higher in the melatonin‐treated mice than in the controls, as were the numbers of primordial, primary, and antral follicles. The mRNA expression of SIRT1 and LC3 and telomere length were enhanced due to melatonin treatment. Seventy‐eight genes that were downregulated during aging and upregulated by melatonin were identified by a microarray analysis. Forty of these 78 genes were ribosome‐related genes, and a free radical scavenging network was identified. The present results indicate that melatonin delays ovarian aging by multiple mechanisms including antioxidant action, maintaining telomeres, stimulating SIRT expression and ribosome function, and by reducing autophagy.

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