Francesco Ragonese1, Lorenzo Monarca2, Antonella De Luca1, Loretta Mancinelli1, Monica Mariani3, Cristina Corbucci3, Sandro Gerli4, Rossana Giulietta Iannitti5, Lucio Leonardi5, Bernard Fioretti6. 1. Department of Chemistry, Biology and Biotechnologies, University of Perugia, Perugia, Italy. 2. Department of Chemistry, Biology and Biotechnologies, University of Perugia, Perugia, Italy; Department of Experimental Medicine, Perugia Medical School, University of Perugia, Perugia, Italy. 3. Centre of Assisted Reproductive Technologies, S. Maria della Misericordia Hospital, Perugia, Italy. 4. Department of Surgical and Biomedical Sciences, Centre of Perinatal and Reproductive Medicine, University of Perugia, Perugia, Italy. 5. S&R Farmaceutici S.p.A Bastia Umbra, Perugia, Italy. 6. Department of Chemistry, Biology and Biotechnologies, University of Perugia, Perugia, Italy. Electronic address: bernard.fioretti@unipg.it.
Abstract
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.
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): Humanovarian 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.
Authors: Rosalia Battaglia; Angela Caponnetto; Anna Maria Caringella; Anna Cortone; Carmen Ferrara; Salvatore Smirni; Rossana Iannitti; Michele Purrello; Giuseppe D'Amato; Bernard Fioretti; Cinzia Di Pietro Journal: Antioxidants (Basel) Date: 2022-05-21