Low Doses of Resveratrol Protect Human Granulosa Cells from Induced-Oxidative Stress

Abstract

Resveratrol is a phytoalexin present in plant-derived foods, including grape’s skin, cocoa, and peanuts. Evidence suggests that it has beneficial effects on human health because of its antioxidant properties. However, there is limited knowledge about the part played by resveratrol in ovarian function. In this paper, the influence of resveratrol on granulosa cells (GC) was evaluated. In addition to being the main estradiol producers, GC are in direct contact with the oocyte, playing a fundamental role in its growth and development. The cell line COV434 and human granulosa cells (hGC), obtained from women undergoing assisted reproductive technology (ART), were used. GC were treated with resveratrol (0.001–20 μM) at different times (24–72 h). Low concentrations of this compound suggest a protective role, as they tend to reduce ROS/RNS formation after inducement of stress. On the contrary, high concentrations of resveratrol affect GC viability and steroidogenic function. As it may act as a direct modulator of GC oxidative balance, this work may help to clarify the impact of resveratrol on GC and the usefulness of this antioxidant as adjunct to infertility treatments.

The therapeutic effects and mechanisms of action of resveratrol on polycystic ovary syndrome: A comprehensive systematic review of clinical, animal and in vitro studies

“…The authors reported that resveratrol inhibited the expression of p66Shc and the production of ROS ( p < 0.005), malondialdehyde (MDA) ( p = 0.01), transforming growth factor‐beta (TGF‐β) ( p < 0.001) and also increased the expression of sirtuin 1 (SIRT1) ( p < 0.001) and superoxide dismutase (SOD) ( p = 0.004) in both granulosa and theca cells. Moreira‐Pinto et al 23 found that resveratrol can play a main role in the prevention of ROS formation ( p < 0.005) in cell line COV434 and human granulosa cells. In addition, Ortega et al 24 investigated the effects of resveratrol on theca‐interstitial cells.…”

The role of macrophages phenotypes in the activation of resolution pathways within human granulosa cells

“…The remaining FF was transferred to 100 mL polypropylene tubes and stored at 37ºC for a maximum of 2 h until sample processing. hGCs were isolated and cultured independently according to the protocol previously published by Moreira-Pinto et al [ 15 ], with some modifications. Briefly, FF samples were centrifuged at 350 g at 10 °C for 10 min.…”

Mitochondria Biology in Reproductive Function

“…Moreover, randomized control trials are required to overcome uncertainties regarding dose and duration of clinical application of antioxidant strategies [ 10 ]. The importance of proper antioxidant supplementation is further supported by data obtained by Moreira-Pinto et al [ 11 ], who show that different concentrations of resveratrol may have contrasting effects on granulosa cells (GCs). Indeed, the authors demonstrated that, although ATP production and membrane mitochondrial potential remained unaffected by any concentration, low resveratrol concentrations have a protective role on GCs by reducing reactive species formation after stress induction, while high concentrations negatively affect GC viability and steroidogenic function [ 11 ].…”

“…The importance of proper antioxidant supplementation is further supported by data obtained by Moreira-Pinto et al [ 11 ], who show that different concentrations of resveratrol may have contrasting effects on granulosa cells (GCs). Indeed, the authors demonstrated that, although ATP production and membrane mitochondrial potential remained unaffected by any concentration, low resveratrol concentrations have a protective role on GCs by reducing reactive species formation after stress induction, while high concentrations negatively affect GC viability and steroidogenic function [ 11 ]. Interestingly, Battaglia et al [ 12 ] demonstrated that oral administration of resveratrol for 3 months prior to IVF can have beneficial effects on oocyte competence in reproductively aged women.…”