title: Myofibroblasts Are Evidence of Chronic Tissue Microtrauma at the Endometrial-Myometrial Junctional Zone in Uteri With Adenomyosis.
abstract: Adenomyosis (AM) uteri exhibit hyperperistalsis. The latter causes a chronic tissue trauma at the endometrial-myometrial junctional zone (EMJZ). Upon tissue trauma, microdehiscences in the myometrium facilitate the translocation of basal endometrial fragments into the myometrium. There, a metaplasia (mediated by transforming growth factor β1 [TGFβ1] and connective tissue growth factor [CTGF]) occurs and AM lesions develop. The abundance of myofibroblasts in a tissue hallmarks metaplasia and points to a tissue microtrauma.
  
  
  
  To study if myofibroblasts-as an evidence of tissue microtrauma-are more abundant at EMJZ in AM-uteri, a case-control experimental study was carried out at Charité University Hospital-Endometriosis Research Centre. In all, 18 uteri with AM and 14 uteri without AM were obtained during laparoscopy-assisted vaginal hysterectomy. The immunolabeling of myofibroblastic metaplasia (alpha smooth muscle actin [ASMA] and collagen I), differentiated smooth muscle marker (desmin) and metaplasia mediators (TGF-β receptors 1, 2, 3 and CTGF) was investigated. The ultrastructure of myofibroblasts at EMJZ of AM uterus was characterized by transmission electron microscopy, in addition to an in vitro study to characterize myofibroblasts in the endometrium of non-AM uterus.
  
  
  
  Immunolabeling of ASMA and collagen I was significantly higher at EMJZ of AM uteri versus non-AM uteri. Furthermore, myofibroblasts were ultrastructurally characterized at EMJZ of AM. Endometrium of non-AM uterus exhibited 5% to 8% of its cells, expressing ASMA and collagen I. No difference was noted regarding metaplasia mediators immunolabeling between both the groups.
  
  
  
  The abundant and persistent myofibroblasts (expressing ASMA/collagen I) at EMJZ in AM uteri are ultra-/microscopic evidence of chronic tissue trauma. They are of nonmyometrial origin, as they lack desmin immunolabeling.
authors.affiliation: 1 Clinic for Gynaecology, Charité University of Medicine, Hindenburgdamm, Berlin, Germany.
authors.forename: Mohamed Gamal
authors.initials: MG
authors.lastname: Ibrahim
authors.affiliation: 2 Praxisklinik am Rosengarten, Augustaanlage, Mannheim, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Sillem
authors.affiliation: 3 Department of Veterinary Medicine, Institute of Veterinary Anatomy, Free University of Berlin, Berlin, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Plendl
authors.affiliation: 1 Clinic for Gynaecology, Charité University of Medicine, Hindenburgdamm, Berlin, Germany.
authors.forename: Vito
authors.initials: V
authors.lastname: Chiantera
authors.affiliation: 1 Clinic for Gynaecology, Charité University of Medicine, Hindenburgdamm, Berlin, Germany.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: 1 Clinic for Gynaecology, Charité University of Medicine, Hindenburgdamm, Berlin, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Mechsner
mesh_terms: D000199:Actins / Q000378:metabolism; D062788:Adenomyosis / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003893:Desmin / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology*; D009215:Myometrium / Q000378:metabolism / Q000473:pathology*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000199:Actins; D015415:Biomarkers; C526317:CCN2 protein, human; D003893:Desmin; D018125:Receptors, Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor
keywords: adenomyosis pathogenesis; collagen I; endometrial–myometrial junctional zone; microtrauma; myofibroblasts