Sphingosine pathway deregulation in endometriotic tissues

Fertil Steril. 2012 Apr;97(4):904-11. doi: 10.1016/j.fertnstert.2011.12.051. Epub 2012 Jan 24.

Abstract

Objective: To investigate key genes expression of the sphingosine-1-phosphate pathway in endometriotic tissues.

Design: A case-control laboratory study.

Setting: Tertiary care university hospital.

Patient(s): A total of 31 women, with (n = 16) and without (n = 15) endometriosis took part in the study.

Intervention(s): After surgical excision with pathological analysis, endometrial specimens were obtained from women affected or not by endometriosis.

Main outcome measure(s): 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.

Result(s): 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.

Conclusion(s): 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.

MeSH terms

  • Aldehyde-Lyases / genetics
  • Analysis of Variance
  • Case-Control Studies
  • Endometriosis / genetics
  • Endometriosis / metabolism*
  • Endometrium / chemistry*
  • Female
  • Hospitals, University
  • Humans
  • Immunohistochemistry
  • Lysophospholipids / metabolism*
  • Membrane Proteins / genetics
  • Ovarian Diseases / genetics
  • Ovarian Diseases / metabolism*
  • Paris
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • RNA, Messenger / analysis
  • Real-Time Polymerase Chain Reaction
  • Receptors, Lysosphingolipid / analysis
  • Receptors, Lysosphingolipid / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism
  • Sphingosine-1-Phosphate Receptors

Substances

  • Lysophospholipids
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Lysosphingolipid
  • S1PR1 protein, human
  • S1PR2 protein, human
  • Sphingosine-1-Phosphate Receptors
  • sphingosine 1-phosphate
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase
  • SGPP1 protein, human
  • SGPP2 protein, human
  • Phosphoric Monoester Hydrolases
  • Aldehyde-Lyases
  • sphingosine 1-phosphate lyase (aldolase)
  • Sphingosine