Role of estrogen receptors in menstrual cycle–related neoangiogenesis and their influence on endothelial progenitor cell physiology

• Published in: Fertility and sterility Vol. 93; no. 1; pp. 220 - 228
• Main Authors: Foresta, Carlo, M.D, De Toni, Luca, B.S, Di Mambro, Antonella, M.D, Ferlin, Alberto, M.D, Perilli, Lisa, B.S, Bertuzzi, Ilaria, B.S, Galan, Alessandro, M.D, Zuccarello, Daniela, M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2010; Elsevier
• Subjects: Adult; Biological and medical sciences; Case-Control Studies; Cells, Cultured; CXCR4; Endometrium - blood supply; Endothelial Cells - immunology; Endothelial Cells - metabolism; Endothelial progenitor cell; Estradiol - blood; estrogen receptor; Estrogen Receptor alpha - blood; Estrogen Receptor alpha - genetics; Estrogen Receptor beta - blood; Estrogen Receptor beta - genetics; Female; Flow Cytometry; Fluorescent Antibody Technique; Gynecology. Andrology. Obstetrics; Humans; Immunoassay; Internal Medicine; Male; Matrix Metalloproteinase 9 - genetics; Medical sciences; Menopause - blood; menstrual cycle; Menstrual Cycle - metabolism; Middle Aged; MMP9; Neovascularization, Physiologic; Obstetrics and Gynecology; Receptors, CXCR4 - blood; Receptors, CXCR4 - genetics; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells - immunology; Stem Cells - metabolism; Time Factors; Young Adult; CXCR4; Endothelial progenitor cell; estrogen receptor; MMP9; menstrual cycle; Estrogen receptor; Endothelial cell; Menstrual cycle; Gynecology; Physiology; Obstetrics; CXCR4 chemokine receptor; Progenitor cell; Hormonal receptor
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2008.09.059

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. Design Quantification of circulating progenitor cells, EPCs, and relative CXCR4+ fraction by flow cytometry. Quantification of plasma 17β-E2 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. Setting University clinic and academic research laboratory. Patient(s) 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). Intervention(s) Blood (35 mL) was collected at each observation point. Main Outcome Measure(s) Correlation between 17β-E2 exposure and neoangiogenesis markers. Result(s) 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-β+ and CXCR4+ EPCs increased during the ovulatory phase, and this increase is probably mediated by ER-β and matrix metalloproteinase 9. Conclusion(s) 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).