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

Am J Reprod Immunol. 2020 Jan;83(1):e13186. doi: 10.1111/aji.13186. Epub 2019 Nov 3.


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-1β, 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-1β, 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.

Keywords: endoplasmic reticulum stress; inflammation; polycystic ovary syndrome; resveratrol.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 4 / genetics
  • Activating Transcription Factor 6 / genetics
  • Adolescent
  • Adult
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • C-Reactive Protein / analysis
  • Cells, Cultured
  • Cumulus Cells / drug effects
  • Cumulus Cells / metabolism
  • Cytokines / blood
  • Double-Blind Method
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress / drug effects
  • Endoplasmic Reticulum Stress / genetics
  • Female
  • Heat-Shock Proteins / genetics
  • Humans
  • NF-kappa B / blood
  • Polycystic Ovary Syndrome* / blood
  • Polycystic Ovary Syndrome* / drug therapy
  • Polycystic Ovary Syndrome* / genetics
  • Resveratrol / pharmacology*
  • Resveratrol / therapeutic use
  • Transcription Factor CHOP / genetics
  • X-Box Binding Protein 1 / genetics
  • Young Adult


  • ATF4 protein, human
  • ATF6 protein, human
  • Activating Transcription Factor 6
  • Anti-Inflammatory Agents
  • Cytokines
  • DDIT3 protein, human
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • NF-kappa B
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Activating Transcription Factor 4
  • Transcription Factor CHOP
  • C-Reactive Protein
  • Resveratrol