Effects of resveratrol on growth and function of rat ovarian granulosa cells

Israel Ortega, Donna H. Wong, Jesus A. Villanueva, Amanda B. Cress, Anna Sokalska, Scott D. Stanley, Antoni J. Duleba

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Objective: To evaluate the effects of resveratrol on growth and function of granulosa cells. Previously, we demonstrated that resveratrol exerts profound proapoptotic effects on theca-interstitial cells. Design: In vitro study. Setting: Research laboratory. Animal(s): Immature Sprague-Dawley female rats. Intervention(s): Granulosa cells were cultured in the absence or presence of resveratrol. Main Outcome Measure(s): DNA synthesis was determined by thymidine incorporation assay, apoptosis by activity of caspases 3/7, cell morphology by immunocytochemistry, steroidogenesis by mass spectrometry, antimüllerian hormone (AMH), and vascular endothelial growth factor (VEGF) expression by polymerase chain reaction and Western blot. Result(s): Resveratrol induced a biphasic effect on DNA synthesis, whereby a lower concentration stimulated thymidine incorporation and higher concentrations inhibited it. Additionally, resveratrol slightly increased the cell number and modestly decreased the activity of caspases 3/7 with no effect on cell morphology or progesterone production. However, resveratrol decreased aromatization and VEGF expression, whereas AMH expression remained unaltered. Conclusion(s): Resveratrol, by exerting cytostatic but not cytotoxic effects, together with antiangiogenic actions mediated by decreased VEGF in granulosa cells, may alter the ratio of theca-to-granulosa cells and decrease vascular permeability, and therefore may be of potential therapeutic use in conditions associated with highly vascularized theca-interstitial hyperplasia and abnormal angiogenesis, such as those seen in women with polycystic ovary syndrome.

Original languageEnglish
Pages (from-to)1563-1573
Number of pages11
JournalFertility and Sterility
Volume98
Issue number6
DOIs
StatePublished - Dec 2012

Keywords

  • AMH
  • Apoptosis
  • VEGF
  • granulosa cells
  • proliferation
  • resveratrol
  • steroidogenesis

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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