title: Structural modifications of the prostate in hypoxia, oxidative stress, and chronic ischemia.
abstract: OBJECTIVE
  Clinical studies have reported a correlation between pelvic ischemia and voiding dysfunction in elderly men. The aim of this study was to identify and compare prostate structural modifications in cultured cells and in a rabbit model after exposure to hypoxia, oxidative stress, and chronic ischemia.
  
  
  METHODS
  Cultured human prostate smooth muscle cells (SMCs), epithelial cells (ECs), and stromal cells (SCs) were incubated under normoxia, hypoxia, and oxidative stress conditions by use of a computerized oxycycler system. We developed a rabbit model of chronic prostate ischemia by creating aorto-iliac arterial atherosclerosis. Markers of oxidative stress were examined by using fluorometric analysis and enzyme immunoassay. Prostate structure was examined by using Masson's trichrome staining and transmission electron microscopy (TEM).
  
  
  RESULTS
  Lipid peroxidation was found in SMCs exposed to hypoxia and in all cell types exposed to oxidative stress. We identified protein oxidation in ECs exposed to hypoxia and in all cell types exposed to oxidative stress. Markers indicating oxidative damage were present in chronically ischemic rabbit prostate tissue. These reactions were associated with DNA damage. Prostate ischemia resulted in epithelial atrophy, loss of smooth muscle, and diffuse fibrosis. TEM showed swollen mitochondria with degraded cristae, loss of membrane, loss of Golgi bodies, degenerated nerves, and disrupted cell-to-cell junctions.
  
  
  CONCLUSIONS
  Human prostate cells exhibited differential reactions to hypoxia and oxidative stress with widespread DNA damage. Structural modifications in ischemic prostate tissue were similar to those in cells exposed to oxidative stress. Structural changes due to ischemia and oxidative stress may contribute to prostatic noncompliance in aging men.
authors.affiliation: Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA.
authors.forename: Portia
authors.initials: P
authors.lastname: Thurmond
authors.affiliation: Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Yang
authors.affiliation: Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA.
authors.forename: Yedan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA.
authors.forename: Lori B
authors.initials: LB
authors.lastname: Lerner
authors.affiliation: Department of Urology and Department of Pathology, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA.
authors.forename: Kazem M
authors.initials: KM
authors.lastname: Azadzoi
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000150:complications; D015415:Biomarkers; D002478:Cells, Cultured; D004249:DNA Damage; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000648:ultrastructure; D005355:Fibrosis; D006801:Humans; D000860:Hypoxia / Q000150:complications*; D007511:Ischemia / Q000150:complications*; D015227:Lipid Peroxidation; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000648:ultrastructure; D009410:Nerve Degeneration; D018384:Oxidative Stress; D011467:Prostate / Q000033:anatomy & histology* / Q000166:cytology*; D011817:Rabbits; D017154:Stromal Cells / Q000648:ultrastructure; D001748:Urinary Bladder Neck Obstruction / Q000150:complications
chemical_list: D015415:Biomarkers
keywords: Fibrosis; Ischemia; Oxidative stress; Prostate