title: Advanced glycation end products and their receptor contribute to ovarian ageing.
abstract: OBJECTIVE
  Do advanced glycation end products (AGE) and the receptor for advanced glycation end products (RAGE) affect the cells of the human ovarian follicle?
  
  
  CONCLUSIONS
  AGE accumulate on the surface of ovarian granulosa-lutein (GL) cells and monocytes by binding to RAGE and other receptors with possible functional effects on these cells.
  
  
  BACKGROUND
  AGE and RAGE are expressed in granulosa and theca cells, as well as in luteinized cells derived from the ovary.
  
  
  METHODS
  In this prospective cohort study, human follicle fluid-derived cells were isolated from aspirates of ovarian follicles of women who underwent assisted reproduction treatment.
  
  
  METHODS
  Immunofluorescence microscopy and multi-colour flow cytometry were used to determine the presence of AGE and RAGE on the surface of follicular fluid-derived cells and to characterize downstream effects of RAGE activation.
  
  
  RESULTS
  GL cells and ovarian monocytes were found to contain AGE and RAGE and to bind AGE-bovine serum albumin (BSA) in correlation with the patients' chronological age. AGE-BSA and BSA failed to induce significantly the cleavage of caspase-3, phosphorylation of nuclear factor-κB or the binding of annexin V (the latter was marginally increased). AGE-fibronectin was found to induce detachment of cultured GL cells in vitro.
  
  
  CONCLUSIONS
  The impact of AGE and RAGE in the ovary, shown here in cells in culture, remains to be affirmed in clinical settings.
  
  
  CONCLUSIONS
  The ligands of RAGE and their effects in the ovary remain uncertain but this study implies that AGEs in the form of structural long-lived extracellular matrix proteins, rather than soluble AGEs, may play a role in the decline of ovarian function during ageing.
  
  
  BACKGROUND
  The project was funded by the Norwegian Resource Centre for Women's Health, Oslo University Hospital. The authors have no conflicts of interests.
authors.affiliation: Section of Reproductive Medicine, Department of Gynaecology, Oslo University Hospital Rikshospitalet, Box 4950 Nydalen, Oslo 0424, Norway.
authors.forename: Mette Haug
authors.initials: MH
authors.lastname: Stensen
authors.forename: Tom
authors.initials: T
authors.lastname: Tanbo
authors.forename: Ritsa
authors.initials: R
authors.lastname: Storeng
authors.forename: Peter
authors.initials: P
authors.lastname: Fedorcsak
mesh_terms: D005260:Female; D015571:Follicular Fluid / Q000166:cytology; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D010053:Ovary / Q000254:growth & development / Q000502:physiology*; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology*; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine
keywords: advanced glycation end products; assisted reproduction; cell culture; cell signalling; female infertility