BackgroundPCOS is a reproductive hormonal abnormality and a metabolic disorder. It is frequently associated with insulin resistance, hyperandrogenism, chronic inflammation, and oxidative stress. We aim to investigate the potential therapeutic effects of combined therapy of resveratrol and metformin on polycystic ovaries via SIRT1 and AMPK activation.MethodsWistar albino rats were divided into control and experimental (PCOS) groups. DHEA-induced PCOS rats were given resveratrol (20 mg/kg/day), metformin (300 mg/kg/day) and combined therapy. At the end of the experiment, the body and ovarian weight of rats were measured and blood samples were analyzed for FSH, LH, testosterone, AMH, TNF-α and MDA levels. Histopathological evaluation of ovaries were carried out by light and electron microscopy. SIRT1 and AMPK immunreactivity and TUNEL assay were scored. Data were statistically analyzed by SPSS programme.ResultsMetformin and combined treatment groups reduced the body and ovary weights compared to the PCOS group. Serum testosterone levels were significantly higher in the PCOS group than in the control group and this was reduced when PCOS was treated with all but especially resveratrol. All the treatment groups decreased LH, LH/FSH, TNF-α and tissue AMH levels which were induced in the PCOS group, whereas metformin was unable to improve the increased MDA and plasma AMH levels. Treatment with resveratrol and/or metformin ameliorated the elevated number of secondary and atretic follicles and the decreased number of Graafian follicles in the PCOS group, which indicates the effect of the treatments on the maintenance of folliculogenesis. Light and electron microscopic findings supported the analysis of follicular count. Increased number of TUNEL (+) granulosa cells in the PCOS group were reduced significantly in the treatment groups. Resveratrol and metformin increased SIRT1 and AMPK immunreactivity, respectively, compared to the PCOS group.ConclusionsThe results suggest that combined therapy of metformin and resveratrol may improve the weight gain, hormone profile and ovarian follicular cell architecture by inducing antioxidant and antiinflammatory systems via SIRT1 and AMPK activation in PCOS.

The aim of the study was to investigate whether melatonin has a protective effect against diminished ovarian reserve induced by smoking. Material and methods: Seventy-two female Wistar-Albino rats were divided into 6 groups: group I (room air), group II (chronic cigarette smoking), group III (room air + 10 mg/kg subcutaneous melatonin), group IV (room air + 20 mg/ kg subcutaneous melatonin), group V (chronic cigarette smoking + 10 mg/kg subcutaneous melatonin), group VI (chronic cigarette smoking + 20 mg/kg subcutaneous melatonin). For 45 days, rats were exposed to cigarette smoke through a smoking machine, then subcutaneous melatonin was administered. Apoptotic index, immunohistochemical scoring, ovarian follicle counting, ovarian tissue and serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) analyses were carried out. Results: All of the primordial, primary, secondary and mature follicle numbers were found to be significantly lowered in study groups. Increased HSCORE with anti-caspase-3 staining and a high follicular apoptotic index were demonstrated in the smoking group. Serum and ovarian tissue levels of MDA were found to be elevated with smoke exposure whereas lower MDA levels were determined in melatonin treated groups. Serum and tissue levels of SOD, GPx and CAT were shown to be reduced in the smoking group in comparison with melatonin treated and control groups. 20 mg/kg melatonin administration in the smoking group revealed significantly decreased HSCOREs and apoptotic indices. Conclusions: Cigarette smoking has been definitely shown to be associated with impaired ovarian reserve with respect to significantly diminished numbers of primordial, primary, secondary and mature follicles. Dose-related treatment of melatonin in smokers may provide an evidently reduced apoptotic index and improved antioxidant activity in tissue.