Effect of resveratrol and metformin on ovarian reserve and ultrastructure in PCOS: an experimental study

Abstract

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.

Effect of fish oil and telmisartan on dehydroepiandrosterone‐induced polycystic ovarian syndrome in rats: The role of oxidative stress, transforming growth factor beta‐1, and nuclear factor kappa B

“…Except the control group, all rats received subcutaneous injection of DHEA in a dose of 6 mg/100 g body weight once daily for 35 days (Furat Rencber et al., 2018). Control group ( n = 10) received subcutaneous injection of 0.2 ml sesame oil daily for 35 days.…”

Effects of melatonin on ovarian reserve in cigarette smoking: an experimental study

“…Anti-caspase-3 expression intensity of follicular cells was determined by a histological score (HSCORE) method. The intensity of anti-caspase-3 immunostaining was semiquantitatively evaluated by the following categories: 0, no staining; 1+, weak staining; 2+, moderate or intermediate staining; 3+, intense or strong staining [23]. For each tissue section, the HSCORE value was created by summing the percentage of cells that were stained at each intensity category and multiplying that value by the weighted intensity of the staining, using the formula HSCORE = ∑Pi (i + 1), where i is the intensity score, and Pi is the percentage of labeled cells for each intensity within a range of 0-100%.…”

Preconception resveratrol intake against infertility: Friend or foe?

“…32,33 In a rat model of PCOS, resveratrol intake improved the increased number of secondary and atretic follicles and the reduced number of Graafian follicles through antioxidant and anti-inflammatory effects, reducing aberrant elevated levels of testosterone, luteinizing hormone, and anti-Müllerian hormones. 34,35 Advanced glycation end products (AGEs) are generated by the reaction between reducing sugars and proteins, lipids, or nucleic acids, and their accumulation in tissues has been involved in the pathogenesis of various diseases, including diabetes mellitus and PCOS. 36 Methylglyoxal is the most powerful precursor of AGEs.…”