title: Sphingosine pathway deregulation in endometriotic tissues.
abstract: OBJECTIVE
  To investigate key genes expression of the sphingosine-1-phosphate pathway in endometriotic tissues.
  
  
  METHODS
  A case-control laboratory study.
  
  
  METHODS
  Tertiary care university hospital.
  
  
  METHODS
  A total of 31 women, with (n = 16) and without (n = 15) endometriosis took part in the study.
  
  
  METHODS
  After surgical excision with pathological analysis, endometrial specimens were obtained from women affected or not by endometriosis.
  
  
  METHODS
  SPHK1-2, SGPP1-2, SGPL1, SPHKAP, and S1PR1-5 messenger RNA expression by quantitative real-time polymerase chain reaction (PCR) in the endometrium of 15 disease-free women, 16 eutopic and 16 ectopic endometrium of endometriosis-affected women. The S1PR1 and S1PR2 expression were further investigated by immunohistochemistry.
  
  
  RESULTS
  The SGPP2 expression was decreased in eutopic and ectopic endometrium of endometriosis-affected women (1.7- and 16.7-fold, respectively). The SGPP1, weakly expressed in healthy endometrium, is up-regulated in endometriosis-affected women (11.9- and 64.7-fold, respectively), but its expression remains low. The SGPL1 expression was decreased in ectopic endometrium (3.3-fold) and SPHKAP expression was increased in ectopic endometrium (112.6-fold) compared with endometrium of disease-free women. In endometriosis-affected women, S1PR3 expression was decreased in eutopic and ectopic endometrium (2.1- and 6.3-fold, respectively); S1PR2 and S1PR1 expression was increased in eutopic (2.5-fold) and ectopic endometrium (2.6-fold). These increases were confirmed at the protein levels by immunohistochemistry.
  
  
  CONCLUSIONS
  Expression of the enzymes implicated in the regulation of the sphingosine-1-phosphate level balance and of its receptors is overall heavily deregulated in endometriotic lesions in favor of a decreased sphingosine-1-phosphate catabolism. Our results plead for a role of the sphingosine pathway in establishing and survival of endometriotic lesions.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, AP- HP, Groupe Hospitalier Universitaire Ouest, Centre Hospitalier Universitaire Cochin Saint Vincent de Paul, Department of Gynecology Obstetrics II and Reproductive Medicine, Paris, France. pietro.santulli@inserm.fr
authors.forename: Pietro
authors.initials: P
authors.lastname: Santulli
authors.forename: Louis
authors.initials: L
authors.lastname: Marcellin
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Noël
authors.forename: Bruno
authors.initials: B
authors.lastname: Borghese
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fayt
authors.forename: Daniel
authors.initials: D
authors.lastname: Vaiman
authors.forename: Charles
authors.initials: C
authors.lastname: Chapron
authors.forename: Céline
authors.initials: C
authors.lastname: Méhats
mesh_terms: D000446:Aldehyde-Lyases / Q000235:genetics; D000704:Analysis of Variance; D016022:Case-Control Studies; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism*; D004717:Endometrium / Q000737:chemistry*; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007150:Immunohistochemistry; D008246:Lysophospholipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics; D010049:Ovarian Diseases / Q000235:genetics / Q000378:metabolism*; D010297:Paris; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D049349:Receptors, Lysosphingolipid / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors; D000099157:Sphingosine Kinase
chemical_list: D000446:Aldehyde-Lyases; D008246:Lysophospholipids; D008565:Membrane Proteins; D010744:Phosphoric Monoester Hydrolases; D017853:Phosphotransferases (Alcohol Group Acceptor); D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000081025:Sphingosine-1-Phosphate Receptors; D000099157:Sphingosine Kinase; C477362:S1PR1 protein, human; C477522:S1PR2 protein, human; C060506:sphingosine 1-phosphate; C498527:SGPP1 protein, human; C498526:SGPP2 protein, human; C022649:sphingosine 1-phosphate lyase (aldolase)