Resveratrol depolarizes the membrane potential in human granulosa cells and promotes mitochondrial biogenesis

Resveratrol promotes mitochondrial biogenesis associated with increased ATP production in human granulosa cells. These effects suggest a role for resveratrol in the physiology of the female reproductive system and therefore present important clinical therapeutic implications.

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VOLUME 115, ISSUE 4, P1063-1073

Authors:

Francesco Ragonese, Ph.D., Lorenzo Monarca, M.Sc., Antonella De Luca, Ph.D., Loretta Mancinelli, Ph.D., Monica Mariani, Ph.D., Cristina Corbucci, Ph.D., Sandro Gerli, M.D., Rossana Giulietta Iannitti, Ph.D., Lucio Leonardi, M.Sc., Bernard Fioretti, Ph.D. 

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.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.