title: Adrenomedullin and vascular endothelial growth factor production by follicular fluid macrophages and granulosa cells.
abstract: BACKGROUND
  Human follicular fluid contains several substances, such as cytokines and growth factors, which may affect follicular growth and maturation. The present study examines the relative contribution of macrophages and granulosa cells in the production of vascular endothelial growth factor (VEGF) and adrenomedullin in the human ovulatory follicle.
  
  
  METHODS
  Both follicular fluid samples and blood samples were obtained at the time of oocyte retrieval following ovarian stimulation from 20 women undergoing IVF treatment because of male infertility. Human follicular fluid macrophages and luteinized granulosa cells were obtained from pooled follicular fluid of individual patients. Accumulation of VEGF and adrenomedullin in the culture medium of the isolated macrophages and human granulosa cells was determined at variable time intervals ranging from 0 to 48 h. Plasma and follicular fluid concentrations of VEGF and adrenomedullin were also measured.
  
  
  RESULTS
  The follicular fluid concentrations of VEGF and adrenomedullin were significantly higher than those found in plasma. After 48 h, accumulation of VEGF in the culture medium of follicular fluid macrophages was significantly higher than that released in the culture medium of luteinized granulosa cells. In contrast, the production rate of adrenomedullin by follicular fluid macrophages was similar to that found in granulosa cells. VEGF secreted by follicular fluid macrophages increased progressively within 48 h of cell culture. A similar response pattern was observed with the culture medium of luteinized granulosa cells, but with lower production rates.
  
  
  CONCLUSIONS
  This study suggests for the first time that both luteinized granulosa cells and macrophages actively secrete VEGF and adrenomedullin into follicular fluid in the human ovary.
authors.affiliation: Institut Clinic of Gynecology, Obstetrics and Neonatology, Faculty of Medicine-University of Barcelona, Hospital Clinic-Institut d'Investigations Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. jbalasch@medicina.ub.es .
authors.forename: Juan
authors.initials: J
authors.lastname: Balasch
authors.forename: Marta
authors.initials: M
authors.lastname: Guimerá
authors.forename: Olga
authors.initials: O
authors.lastname: Martinez-Pasarell
authors.forename: Josefa
authors.initials: J
authors.lastname: Ros
authors.forename: Juan A
authors.initials: JA
authors.lastname: Vanrell
authors.forename: Wladimiro
authors.initials: W
authors.lastname: Jiménez
mesh_terms: D053607:Adrenomedullin; D000328:Adult; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D005260:Female; D015571:Follicular Fluid / Q000166:cytology* / Q000378:metabolism*; D006107:Granulosa Cells / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D034461:Luteinization / Q000502:physiology; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology; D009994:Osmolar Concentration; D010455:Peptides / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism
chemical_list: D003470:Culture Media; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D053607:Adrenomedullin