Beneficial Role of Resveratrol on Oxidative Stress in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial

Abstract

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder in women. Oxidative stress (OS) plays a pivotal role in the pathogenesis of PCOS. Resveratrol, as a natural polyphenol, has several beneficial therapeutic effects for women with PCOS. In this study, we investigated the antioxidant effect of resveratrol on OS markers in follicular fluid (FF) and granulosa cells (GCs) of patients with PCOS. A total of fifty-six patients with PCOS were randomly assigned to receive 800 mg/day of resveratrol or placebo for 60 days. The main focus was on evaluating OS markers, such as malondialdehyde (MDA) and total thiol (sulfhydryl) content in FF, along with assessing the levels of total antioxidant capacity (TAC) and total oxidant status (TOS) in GCs. Additionally, secondary outcomes included measuring the expression of genes associated with OS responses (Manganese superoxide dismutase (Mn-SOD), catalase (CAT), and uncoupling protein 2 (UCP2)), as well as the expression of UCP2 protein in granulosa cells. Compared with the placebo group, resveratrol reduced MDA and conversely significantly increased total thiol (P = 0.6694 and P = 0.0318, respectively) in FF. Resveratrol significantly reduced TOS and oxidative stress index (OSI) (P = 0.0299 and P = 0.0144, respectively) and significantly increased TAC (P = 0.0484) in GCs. There were significant increases in CAT and UCP2 expression after resveratrol consumption (P = 0.0158 and P = 0.0004, respectively). Although resveratrol increased Mn-SOD expression (P = 0.0914), its effects were not statistically significant. Resveratrol significantly affected UCP2 protein levels (P = 0.0030). These findings suggested that 60 days of supplementation with 800 mg/day resveratrol improves markers of OS in the FF and GCs of patients with PCOS. Trial registration number: http://www.irct.ir ; IRCT20221106056417N1; 2023 February 09.

Keywords: Follicular fluid; Granulosa cells; Oxidative stress; Polycystic ovary syndrome (PCOS); Resveratrol.