Samaneh Brenjian1, Ashraf Moini2,3,4, Nazila Yamini5, Ladan Kashani2, Maryam Faridmojtahedi2, Mojdeh Bahramrezaie1, Mahshad Khodarahmian1, Fardin Amidi1,6. 1. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2. Department of Gynecology and Obstetrics, School of Medicine, Tehran University of Medical Science, Tehran, Iran. 3. Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. 4. Vali-e-Asr Reproductive Health Research Center, Tehran University of Medical Sciences, Tehran, Iran. 5. Embryology Laboratory, Department of ART, Arash Women's Hospital, Tehran University of Medical Science, Tehran, Iran. 6. Department of Infertility, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
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.
RCT Entities:
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.
Authors: Amir Ajoolabady; Simin Liu; Daniel J Klionsky; Gregory Y H Lip; Jaakko Tuomilehto; Sina Kavalakatt; David M Pereira; Afshin Samali; Jun Ren Journal: Trends Pharmacol Sci Date: 2021-12-08 Impact factor: 14.819
Authors: Jacqueline T Hecht; Alka C Veerisetty; Juliana Wu; Francoise Coustry; Mohammad G Hossain; Frankie Chiu; Francis H Gannon; Karen L Posey Journal: Am J Pathol Date: 2021-06-08 Impact factor: 5.770