title: Autophagy is upregulated in ovarian endometriosis: a possible interplay with p53 and heme oxygenase-1.
abstract: OBJECTIVE
  To evaluate the occurrence of the autophagic process in ovarian endometriomas compared with eutopic endometrium of affected women and with normal endometrium of healthy women.
  
  
  METHODS
  Biochemical and molecular study in tissue extracts.
  
  
  METHODS
  University cellular pathology laboratory and university hospital.
  
  
  METHODS
  Patients with ovarian endometriosis (n = 13) and healthy women (n = 18).
  
  
  METHODS
  Specimens of endometrium were obtained by hysteroscopy from patients with endometriosis and from healthy control subjects; specimens of ovarian endometriomas were collected by laparoscopy. All patients underwent surgery after the end of menstrual bleeding, resulting in most of our patients (approximately 80% in each group) being in the proliferative phase.
  
  
  METHODS
  Autophagy was evaluated by Western blot analysis of biochemical markers (LC3-II, LC3-II/LC3-I ratio and p62) and by quantitative real-time polymerase chain reaction of autophagy-related genes (ATG14, BECN1, ATG7, and LC3B); apoptosis-related (p53 and Bcl-2) and oxidative stress-related (heme oxygenase-1) proteins were also evaluated by Western blot analysis.
  
  
  RESULTS
  All tested biochemical markers and messenger RNA levels of autophagy-related genes showed a significant up-regulation of autophagy in ovarian endometriomas compared with eutopic endometria of affected or healthy women. Moreover, a significant decrease of p53 protein and a significant increase of heme oxygenase-1 protein was also evident in endometriomas.
  
  
  CONCLUSIONS
  The upregulated autophagic process observed in ovarian endometriomas can be regarded as an integral part of endometriosis pathogenesis, possibly contributing to survival of endometriotic cells in ectopic sites and to lesion maintenance. The decreased susceptibility to apoptosis and the persistent oxidative stress experienced by endometriotic cells could favor autophagy stimulation.
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Allavena
authors.affiliation: Obstetrics and Gynecology Unit, Department of Molecular and Developmental Medicine, "S. Maria alle Scotte" Hospital, University of Siena, Siena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Carrarelli
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Del Bello
authors.affiliation: Obstetrics and Gynecology Unit, Department of Molecular and Developmental Medicine, "S. Maria alle Scotte" Hospital, University of Siena, Siena, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Luisi
authors.affiliation: Obstetrics and Gynecology Unit, Department of Molecular and Developmental Medicine, "S. Maria alle Scotte" Hospital, University of Siena, Siena, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy; Istituto Toscano Tumori, Florence, Italy. Electronic address: emilia.maellaro@unisi.it.
authors.forename: Emilia
authors.initials: E
authors.lastname: Maellaro
mesh_terms: D000328:Adult; D001343:Autophagy / Q000235:genetics; D016022:Case-Control Studies; D004715:Endometriosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D005260:Female; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000032:analysis* / Q000235:genetics; D006785:Hospitals, University; D006801:Humans; D010053:Ovary / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: Autophagy; heme oxygenase-1; ovarian endometriosis; p53