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Resveratrol depolarizes the membrane potential in human granulosa cells and promotes mitochondrial biogenesis
Fertility and Sterility ( IF 6.7 ) Pub Date : 2021-01-01 , DOI: 10.1016/j.fertnstert.2020.08.016
Francesco Ragonese 1 , Lorenzo Monarca 2 , Antonella De Luca 1 , Loretta Mancinelli 1 , Monica Mariani 3 , Cristina Corbucci 3 , Sandro Gerli 4 , Rossana Giulietta Iannitti 5 , Lucio Leonardi 5 , Bernard Fioretti 1
Affiliation  

OBJECTIVE To study the biological effects of resveratrol on the growth, electrophysiology, and mitochondrial function of human granulosa cells (h-GCs). DESIGN Preclinical study. SETTING Electrophysiology laboratory and in vitro fertilization unit. PATIENT(S) This study included h-GCs from seven infertile women undergoing assisted reproductive techniques. INTERVENTION(S) Human ovarian Granulosa Cell Tumor (GCT) cell line COV434 and h-GCs obtained after oocyte retrieval were cultured in the absence or presence of resveratrol. MAIN OUTCOME MEASURE(S) Granulosa cells were evaluated for cell viability and mitochondrial activity. Electrophysiological recordings and evaluation of potassium current (IKur) and Ca2+ concentration were also performed. RESULT(S) Resveratrol induced mitochondrial activity in a bell-shaped, dose-effect-dependent manner. Specifically, resveratrol treatment (3 μM, 48 hours) increased ATP production and cell viability and promoted the induction of cellular differentiation. These biological changes were associated with mitochondrial biogenesis. Electrophysiological recordings showed that resveratrol reduced the functional expression of an ultra rapid activating, slow inactivating, delayed rectifier potassium current (IKur) that is associated with a plasma membrane depolarization and that promotes an increase in intracellular Ca2+. CONCLUSION(S): The effects of resveratrol on potassium current and mitochondrial biogenesis in h-GCs could explain the beneficial effects of this polyphenol on the physiology of the female reproductive system. These findings suggest there are therapeutic implications of resveratrol in a clinical setting.

中文翻译:

白藜芦醇使人颗粒细胞的膜电位去极化并促进线粒体生物发生

目的研究白藜芦醇对人颗粒细胞(h-GCs)生长、电生理和线粒体功能的生物学影响。设计 临床前研究。设置电生理实验室和体外受精单元。患者 本研究包括来自七名接受辅助生殖技术的不孕妇女的 h-GC。干预 在不存在或存在白藜芦醇的情况下培养人卵巢颗粒细胞肿瘤 (GCT) 细胞系 COV434 和取卵后获得的 h-GC。主要结果测量评估颗粒细胞的细胞活力和线粒体活性。还进行了电生理记录和钾电流 (IKur) 和 Ca2+ 浓度的评估。结果 白藜芦醇以钟形、剂量效应依赖性方式诱导线粒体活性。具体而言,白藜芦醇处理(3 μM,48 小时)增加了 ATP 产生和细胞活力,并促进了细胞分化的诱导。这些生物学变化与线粒体生物发生有关。电生理记录显示,白藜芦醇降低了与质膜去极化相关的超快速激活、缓慢失活、延迟整流钾电流 (IKur) 的功能表达,并促进细胞内 Ca2+ 的增加。结论(S):白藜芦醇对 h-GCs 中钾电流和线粒体生物发生的影响可以解释这种多酚对女性生殖系统生理的有益影响。这些发现表明白藜芦醇在临床环境中具有治疗意义。48 小时)增加 ATP 产量和细胞活力,并促进细胞分化的诱导。这些生物学变化与线粒体生物发生有关。电生理记录显示,白藜芦醇降低了与质膜去极化相关的超快速激活、缓慢失活、延迟整流钾电流 (IKur) 的功能表达,并促进细胞内 Ca2+ 的增加。结论(S):白藜芦醇对 h-GCs 中钾电流和线粒体生物发生的影响可以解释这种多酚对女性生殖系统生理的有益影响。这些发现表明白藜芦醇在临床环境中具有治疗意义。48 小时)增加 ATP 产量和细胞活力,并促进细胞分化的诱导。这些生物学变化与线粒体生物发生有关。电生理记录显示,白藜芦醇降低了与质膜去极化相关的超快速激活、缓慢失活、延迟整流钾电流 (IKur) 的功能表达,并促进细胞内 Ca2+ 的增加。结论(S):白藜芦醇对 h-GCs 中钾电流和线粒体生物发生的影响可以解释这种多酚对女性生殖系统生理的有益影响。这些发现表明白藜芦醇在临床环境中具有治疗意义。
更新日期:2021-01-01
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