title: Effects of resveratrol on growth and function of rat ovarian granulosa cells.
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.
  
  
  METHODS
  In vitro study.
  
  
  METHODS
  Research laboratory.
  
  
  METHODS
  Immature Sprague-Dawley female rats.
  
  
  METHODS
  Granulosa cells were cultured in the absence or presence of resveratrol.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, University of California, Davis, California 95817, USA.
authors.forename: Israel
authors.initials: I
authors.lastname: Ortega
authors.forename: Donna H
authors.initials: DH
authors.lastname: Wong
authors.forename: Jesus A
authors.initials: JA
authors.lastname: Villanueva
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Cress
authors.forename: Anna
authors.initials: A
authors.lastname: Sokalska
authors.forename: Scott D
authors.initials: SD
authors.lastname: Stanley
authors.forename: Antoni J
authors.initials: AJ
authors.lastname: Duleba
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006107:Granulosa Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D020533:Angiogenesis Inhibitors; D013267:Stilbenes; D000077185:Resveratrol