Resveratrol treatment in patients with polycystic ovary syndrome decreased pro-inflammatory and endoplasmic reticulum stress markers.

PROBLEM: Polycystic ovary syndrome (PCOS) is associated with endoplasmic reticulum (ER) stress and pro-inflammatory condition. The aim of the present study was to evaluate the effect of resveratrol treatment on pro-inflammatory and ER stress markers in patients with PCOS. METHOD OF STUDY: Cumulus cells were obtained from 40 patients with PCOS who were divided into two groups: placebo and resveratrol treatment (receiving 800 mg/d for 40 days) groups. Blood samples were obtained from all patients before and after the procedure to evaluate interleukin (IL)-6, IL-1ß, IL-18, TNF-α, NF-κB, and C-reactive protein (CRP). Total RNA was extracted from cumulus cells, and cDNA was synthesized by reverse transcription. Expressions of five genes in ER stress response pathway (ATF4, ATF6, CHOP, GRP78, and XBP1s) were assessed with quantitative real-time PCR. Statistical analysis was performed with Student's t test. RESULTS: After treatment with resveratrol, it was found that serum levels of IL-6, IL-1ß, TNF-α, IL-18, NF-κB, and CRP decreased in the treatment group. In addition, gene expression results showed that the expression levels of ATF4 (P < .05) and ATF6 (P < .001) significantly increased in the resveratrol treatment group, while the expression levels of CHOP, GRP78, and XBP1 (P < .001 for all) significantly decreased. CONCLUSION: Results demonstrated that resveratrol has anti-inflammatory effects through the suppression of NF-κB and NF-κB-regulated gene products. On the other hand, resveratrol can modulate ER stress in granulosa cells (GCs) by altering the expression of genes involved in unfolding protein response (UPR) process. Our findings suggest that ER stress is a potential therapeutic target for patients with PCOS.

Effects of resveratrol on VEGF & HIF1 genes expression in granulosa cells in the angiogenesis pathway and laboratory parameters of polycystic ovary syndrome: a triple-blind randomized clinical trial.

OBJECTIVES: Management options for PCOS, as the most prevalent endocrine disorder in women of reproductive age, using natural supplements have a high priority for physicians, especially based on the etiological pathways. Therefore, this study was conducted to describe the effect of resveratrol on the angiogenesis pathway, for management of PCOS through assessing VEGF, HIF1 gene expression, and laboratory parameters. METHODS: In this triple-blind RCT, PCOS was confirmed in ICSI candidates based on the Rotterdam criteria. Sixty-two patients that met the inclusion criteria were randomly assigned to two groups. All patients took resveratrol 800 mg/day or placebo for 40 days orally from the beginning of their previous menstruation cycle until the oocyte retrieval day. The serum levels of different hormones were measured, and the expression of HIF1 & VEGF genes was quantified by real-time PCR. RESULTS: As for the laboratory hormone assay in 61 PCOS patients, a significant mean difference was seen in the FSH, LH, TSH, and testosterone between the two groups (P < 0.05). The results showed a reduction in the expression of VEGF & HIF1 genes under the effect of resveratrol in the granulosa cells (P = 0.0001). The number of mature oocytes, cleavage rate, fertilization rate, and fertility rate were not significantly different between the two groups (P > 0.05), but the high-quality oocyte rate and high-quality embryo rate were higher in the resveratrol group (P < 0.05). CONCLUSIONS: Based on the results, resveratrol may improve some outcomes of PCOS patients, probably through changing the serum levels of some sex hormones and expression of VEGF & HIF1 genes in the angiogenesis pathway of granulosa cells.