title: The distinguishing cellular and molecular features of the endometriotic ovarian cyst: from pathophysiology to the potential endometrioma-mediated damage to the ovary.
abstract: BACKGROUND
  Clinical data suggest that the presence of an ovarian endometrioma may cause per se damage to the surrounding otherwise healthy ovarian tissue. However, the basic research has so far done a limited job in trying to understand the potential detrimental effect of an endometrioma presence in the context of the ovarian physiology. We have reviewed the literature with the aim of characterizing the pathophysiology of the endometrioma focusing mostly on factors and mechanisms potentially affecting the surrounding, otherwise normal, ovarian tissue.
  
  
  METHODS
  Comprehensive searches of PUBMED were conducted to identify human studies published from 1991 to 2013 in the English language on the cellular and molecular characterization of the various endometrioma components.
  
  
  RESULTS
  An endometrioma contains free iron, reactive oxygen species (ROS), proteolytic enzymes and inflammatory molecules in concentrations from tens to hundreds of times higher than those present in peripheral blood or in other types of benign cysts. The cyst fluid causes substantial changes in the endometriotic cells that it baths from gene expression modifications to genetic mutations The physical barrier between the cyst contents and the normal ovarian tissue is a thin wall composed of the ovarian cortex itself or fibroreactive tissue. ROS potentially permeating the surrounding tissues and proteolytic substances degrading the adjacent areas are likely to cause the substitution of normal ovarian cortical tissue with fibrous tissue in which the cortex-specific stroma is reduced. The fibrosis is associated with smooth muscle metaplasia and followed by follicular loss and intraovarian vascular injury. Follicular density in tissue surrounding the endometriotic cyst was consistently shown to be signiﬁcantly lower than in healthy ovaries but this pathological change does not appear to be caused by the stretching of surrounding tissues owing to the presence of a cyst.
  
  
  CONCLUSIONS
  There is sufficient molecular, histological and morphological evidence, in part deriving from knowledge of the pathophysiology, to support a deleterious effect of the endometrioma on the adjacent ovarian cortical tissue, independent of the mere mechanical stretching owing to its size.
authors.affiliation: Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Sanchez
authors.forename: P
authors.initials: P
authors.lastname: Viganò
authors.forename: E
authors.initials: E
authors.lastname: Somigliana
authors.forename: P
authors.initials: P
authors.lastname: Panina-Bordignon
authors.forename: P
authors.initials: P
authors.lastname: Vercellini
authors.forename: M
authors.initials: M
authors.lastname: Candiani
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D010048:Ovarian Cysts / Q000378:metabolism / Q000473:pathology*; D006080:Ovarian Follicle / Q000473:pathology; D010053:Ovary / Q000098:blood supply; D010447:Peptide Hydrolases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D007501:Iron; D010447:Peptide Hydrolases
keywords: IVF; endometrioma; ovarian cyst; pathophysiology; vasculature