The effect of kisspeptin administration on mtor (the mammalian target of rapamycin) mechanism in experimentally induced polycycstic over syndrome (PCOS)

Objective: In this study, we aimed to investigate in the experimental policystic over syndrome, the effect of Kisspeptin-10 administration on the ovarian tissue of the mTOR signaling pathway involved in follicle development histochemistry, immunohistochemistry and biochemistry. Method: In our study; Twenty-seven 23-day-old Wistar strain female rats (50-80 g) were used and the subjects were divided into 4 groups: GROUP 1 (Control Group, n = 6): No application was performed to this animals. GROUP 2 (Solvent Group, n = 7): 0.2 ml of sesame oil administered subcutaneously for 20 days and intraperitoneally administered saline solution (0.2 ml) for 20 days. GROUP 3 (PCOS Group, n = 7): In order to establish PKOS model for 20 days; subcutaneously administered with 6 mg / 100 g of DHEA (Dehydroepiandrostenedion) dissolved in 0.2 ml of sesame oil and administered intraperitoneally with saline solution (0.2 ml) for 20 days. GROUP 4 (PCOS+Kisspeptin-10, n = 7): Kisspeptin-10 administered intraperitoneally to 100 nmol for 20 days with subcutaneous 6mg / 100g DHEA dissolved in 0.2 ml of sesame oil to form a PCOS model for 20 days. Blood samples were taken at the beginning of the experiment, on day 20 and at the end of the experiment. Sections for histochemical studies were stained with Hematoxylin-Eosin, Masson Tricrom, Periodic Acid Schiff (PAS). Immunohistochemically stained with mTOR and p-mTOR antibodies. For morphometric examinations; follicle counts, diameters of primary and secondary follicles, and granulosa layer thickness. Blood plasma estradiol and progesterone levels for biochemical studies were examined by ELISA. Differences between the groups were evaluated statistically by Kruskal Wallis and Mann Whitney-U tests. Results: It was observed that the number of cystic and atretic follicles in the PCOS group increased and the vascular structures in the medulla region expanded in histochemical examinations. The amount of collagen was observed to be similar in all groups. In the PCOS+Kisspeptin group, there was a decrease in the number of cystic and atretic follicles according to the PCOS group. In terms of primary follicle diameter, it was observed that there was a decrease in the PCOS group compared to the control group, and as to the secondary follicle diameter, there was an increase in the PCOS group compared to the control group. However, when the PCOS and PCOS+Kisspeptin groups are compared, there was no change in the diameter of the primary follicle, and the diameter of the secondary follicle was increased in the PCOS group. When we examine the thickness of the granulosa layer of the primary follicle; PCOS and PCOS+Kisspeptin group were observed to be decreased according to the control group. There is a decrease in the PCOS group of the saccharide follicle compared to the control group in the granulosa cell layer; It was observed that the granulosa cell layer of PCOS + Kisspeptin group decreased according to the PCOS group. As a result of the immunohistochemical studies made; when the control group was compared with the PCOS group, it was observed that the mTOR immunopositivity decreased in the granulosa cells. In the PCOS + Kisspeptin group, there was a decrease in the number of mTOR positive cells compared to the PCOS group. p-mTOR immunopositivity in the PCOS group; Compared to the control group, it was observed that there was a decrease in PCOS+Kisspeptin group compared to the PCOS group. When biochemically analyzed, it was observed that the levels of estradiol and progesterone were increased in the PCOS group compared to the control group, and that in the PCOS+Kisspeptin group was decreased compared to the PCOS group. Conclusion: Based on the findings of our study; we observed that in the experimental PKOS model, the number of cystic follicles of the Kisspeptin-10 decreased, the efficiency of the mTOR signaling pathway, which is effective in energy metabolism and proliferation in the cell, decreased and the levels of plasma estradiol and progesterone hormones were decreased at high levels. We believe that the application of Kisspeptin-10 in PKOS, a complex disease in these findings, will provide guidance for new studies.