title: Resveratrol and desferoxamine protect human OxLDL-treated granulosa cell subtypes from degeneration.
abstract: BACKGROUND
  Obese women suffer from anovulation and infertility, which are driven by oxidative stress caused by increased levels of lipid peroxides and circulating oxidized low-density lipoprotein (oxLDL). OxLDL binds to lectin-like oxLDL receptor 1 (LOX-1), cluster of differentiation 36 (CD36), and toll-like receptor 4 (TLR4) and causes cell death in human granulosa cells (GCs).
  
  
  OBJECTIVE
  Our objective was to reveal whether treatment with antioxidants resveratrol (RES) and/or desferoxamine (DFO) protect GCs from oxLDL-induced damage.
  
  
  METHODS
  This basic research study was performed at the Institute of Anatomy and the Clinic of Reproductive Medicine.
  
  
  METHODS
  Patients were women undergoing in vitro fertilization therapy.
  
  
  METHODS
  GC cultures were treated with oxLDL alone or with RES or DFO under serum-free conditions for up to 36 hours. Dead cells were determined by propidium iodide uptake, cleaved caspase-3 expression, and electron microscopy. Mitosis was detected by Ki-67 immunostaining. LOX-1, TLR4, CD36, and heat-shock protein 60 were examined by Western blot. Measurement of oxidative stress markers (8-iso-prostaglandin F2α, advanced glycation end products, and protein carbonyl content) was conducted with ELISA kits.
  
  
  RESULTS
  Different subtypes of human GCs exposed to RES or DFO were protected as evidenced by the lack of cell death, enhanced mitosis, induction of protective autophagy, reduction of oxidative stress markers, and reduced expression of LOX-1, TLR4, CD36, and heat-shock protein 60. Importantly, RES could restore steroid biosynthesis in cytokeratin-positive GCs, which exhibited significant induction of steroidogenic acute regulatory protein.
  
  
  CONCLUSIONS
  RES and DFO exert a protective effect on human GCs. Thus, RES and DFO may help improve the treatment of obese women or polycystic ovarian syndrome patients undergoing in vitro fertilization therapy.
authors.affiliation: Institute of Anatomy (U.S., M.N., I.B., H.S.), University of Leipzig, D-04103 Leipzig, Germany; and Clinic for Reproductive Medicine and Gynecological Endocrinology (P.J., V.B.), D-04103 Leipzig, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Schube
authors.forename: M
authors.initials: M
authors.lastname: Nowicki
authors.forename: P
authors.initials: P
authors.lastname: Jogschies
authors.forename: V
authors.initials: V
authors.lastname: Blumenauer
authors.forename: I
authors.initials: I
authors.lastname: Bechmann
authors.forename: H
authors.initials: H
authors.lastname: Serke
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D003676:Deferoxamine / Q000494:pharmacology*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D008077:Lipoproteins, LDL; D013267:Stilbenes; C099252:oxidized low density lipoprotein; D003676:Deferoxamine; D000077185:Resveratrol