title: Role of estrogen receptors in menstrual cycle-related neoangiogenesis and their influence on endothelial progenitor cell physiology.
abstract: OBJECTIVE
  To study whether estrogen receptors (ERs) are expressed in vitro and in vivo by female circulating endothelial progenitor cells (EPCs); and the role of ERs in the periodic vascular damage and repair that occurs during the menstrual cycle.
  
  
  METHODS
  Quantification of circulating progenitor cells, EPCs, and relative CXCR4+ fraction by flow cytometry. Quantification of plasma 17beta-E(2) by electrochemiluminescent immunoassay. Expression of ERs by immunofluorescence and immunohistochemistry. Estrogen receptor, CXCR4, and matrix metalloproteinase 9 gene expression by reverse transcriptase-polymerase chain reaction and real-time polymerase chain reaction.
  
  
  METHODS
  University clinic and academic research laboratory.
  
  
  METHODS
  Twelve young fertile women (aged 22-27 years) observed for 6 months, 10 postmenopausal women (aged 52-63 years), and 50 male control subjects (aged 24-61 years).
  
  
  METHODS
  Blood (35 mL) was collected at each observation point.
  
  
  METHODS
  Correlation between 17beta-E(2) exposure and neoangiogenesis markers.
  
  
  RESULTS
  Estrogen receptors are expressed both in cultured EPCs after prolonged estrogen stimulation and in circulating EPCs, such as in CD34+ cells in bone marrow. The number of ER-beta+ and CXCR4+ EPCs increased during the ovulatory phase, and this increase is probably mediated by ER-beta and matrix metalloproteinase 9.
  
  
  CONCLUSIONS
  Estrogens play a key role in neoangiogenesis processes, such as endometrium recovery, and this mechanism involves both a central action (on bone marrow) and a cytokine-mediated peripheral one (on endothelium).
authors.affiliation: Department of Histology, Microbiology and Medical Biotechnologies, Center for Male Gamete Cryopreservation, University of Padova, Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Foresta
authors.forename: Luca
authors.initials: L
authors.lastname: De Toni
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Mambro
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferlin
authors.forename: Lisa
authors.initials: L
authors.lastname: Perilli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bertuzzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Galan
authors.forename: Daniela
authors.initials: D
authors.lastname: Zuccarello
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D004717:Endometrium / Q000098:blood supply*; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000097:blood* / Q000235:genetics; D047629:Estrogen Receptor beta / Q000097:blood* / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007118:Immunoassay; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008593:Menopause / Q000097:blood; D008597:Menstrual Cycle / Q000378:metabolism*; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D019718:Receptors, CXCR4 / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D055815:Young Adult
chemical_list: C527276:CXCR4 protein, human; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019718:Receptors, CXCR4; D004958:Estradiol; D020780:Matrix Metalloproteinase 9