Investigation of possible effects of exendin-4 during exposure to mild chronic stress on dehydroepiandrosterone-induced polycystic ovary syndrome of rats

Aim: PCOS is a common disorder that affects women of reproductive age. Exposure to chronic stress in PCOS leads to increase in insulin resistance by affecting HPG and HPA axes. In this study development of insulin resistance was observed after establishment of PCOS model via DHEA. The aim of the study is to investigate effects of Exe on rats with insulin resistance and PCOS in chronic mild stress medium. Material and Method: For PCOS model, DHEA (6 mg/100 g) in 0.2 ml sesame oil was applied subcutaneously to 21-days Sprague Dawley rats. In addition, 0.2 ml sesame oil was injected subcutaneously to rats in solution groups. At the beginning stage of the study, rats were grouped as Control, Solution and PCOS, then stress and Exe groups were also considered in the second stage study. In PCOS groups Exe was applied as intraperitonally (10μg/kg/day) in stress medium for four weeks. Effects of Exe in stress medium was investigated by taking blood samples and examining weight, fasting blood glucose, fasting blood insülin, HOMA-IR, LH, FSH and corticosterone levels. Levels of insülin, LH, FSH and corticosterone were measured by ELISA method. Histopathological images of pancreas and ovarium were also examined. Results: Weight, fasting blood glucose, fasting blood insulin and HOMA-IR levels of rats with PCOS were significantly higher than the other groups, also corticosterone levels of stress groups were significantly higher than the other groups. In addition harmful effects of PCOS on ovarian and pancreas tissues were observed in histological examinations. Exe application in PCOS groups decreased weight, fasting blood glucose, fasting blood insulin, HOMA-IR and LH/FSH levels of the groups whereas Exe application in PCOS group treated with stress was not as effective as applying Exe on rats with PCOS. Exe application also increased number of healthy follicles in PCOS group whereas there was no change in number of healthy follicles in PCOS+Stress group. Conclusion: Chronic stress has harmful effects on metabolic diseases like PCOS and limits effects of treatment agents in PCOS.