Sphingosine pathway deregulation in endometriotic tissues

Capsule:
Expression of sphingosine-1-phosphate catabolic enzymes and receptors is altered in endometriosis. These modifications enhance the sphingosine-1-phosphate axis, promoting survival and angiogenesis. This may contribute to the establishment and development of endometriosis.

Authors:
Pietro Santulli, M.D., Louis Marcellin, M.D., Jean-Christophe Noël, M.D., Ph.D., Bruno Borghese, M.D., Ph.D., Isabelle Fayt, M.D., Daniel Vaiman, Ph.D., Charles Chapron, M.D., Céline Méhats, Ph.D.
Volume 97, Issue 4 , Pages 904-911.e5, April 2012

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.

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