Effect of melatonin on PTEN/PI3K/AKT pathway in aged mouse ovarium

The habits that have entered our lives with modern living today, such as poor nutrition, insomnia, stress, and many other conditions, can indirectly lead to infertility. The current living conditions have delayed the age of reproduction. When looking at women's reproductive issues, the accumulated mutations in the body with advancing age and the regular expulsion of oocytes through menstrual cycles cause a gradual decrease in ovarian reserve. When the impact of circadian rhythms in living organisms on cellular activities is examined, it is known that the effect of the endogenous melatonin hormone, whose production is determined by darkness and light, plays a role. In this study, the aim was to investigate the effect of exogenous melatonin hormone, known for its anti-aging and antioxidant properties in the literature, on the PTEN/PI3K/AKT pathway in the ovaries of elderly mice. A total of 48 healthy female Balb/c mice were used in the study, with 24 mice aged 12 weeks and 24 mice aged 20 months. The mice used for the experiment were divided into six groups: Adult Control (AC) Group, Adult Melatonin (AM) Group, YS Adult Sham (AS) Group, Aged Control (AG Control) Group, Aged Melatonin (AG Melatonin) Group, and Aged Sham (AG S) Group. Mice from groups AC and AGC received no treatment for 7 days. Mice from groups AM and AGM were administered melatonin (10mg/kg intraperitoneally) for 7 days. Mice from groups AS and AGS were intraperitoneally administered 10% diluted ethyl alcohol for 7 days. On day 8, mice were administered 200/10 mg/kg ketamine/xylazine intraperitoneally, and then, ovarian tissues were removed. The experiment was terminated by sacrificing the animals using the cervical dislocation method. Histological and immunohistochemical analyses were followed by tissue preservation and blocking procedures. When comparing the AG control group with the AG melatonin group, there was a noticeable increase in the number of follicles. In tissues belonging to sham groups where ethyl alcohol, used as a solvent for melatonin, was applied, there was a significant increase in the number of atretic follicles. In terms of the number of follicles, there was no statistically significant difference between the adult group treated with melatonin and the control group. While PTEN/PI3K/AKT expression did not differ between control and sham in adult groups, it was increased in the melatonin-administered group versus the other two groups in aged ovaries. Further studies are needed to better understand the effects of melatonin on ovarian tissue.