Sphingosine pathway deregulation in endometriotic tissues

Santulli P, Piétro Santulli, Pietro Santulli, Louis Marcellin, Marcellin L, Jean-Christophe Noël, Jean‐Christophe Noël, Noël JC, Borghese B, Bruno Borghese, Isabelle Fayt, Fayt I, Daniel Vaiman, Charles Chapron, Chapron C, Céline Méhats
Fertility and sterility · 2012 · vol. 97(4) , pp. 904–911.e5 · doi:10.1016/j.fertnstert.2011.12.051 · PMID:22277765 · W2146298094
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This paper investigated alterations in the sphingosine pathway within endometriotic tissues, identifying key dysregulations.

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Abstract

ObjectiveTo investigate key genes expression of the sphingosine-1-phosphate pathway in endometriotic tissues.DesignA case-control laboratory study.SettingTertiary 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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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Lysophospholipids Ovarian Diseases Sphingosine Aldehyde-Lyases Aldehyde-Lyases Analysis of Variance Case-Control Studies Endometriosis Endometriosis Endometrium Female Hospitals, University Humans Immunohistochemistry Lysophospholipids Membrane Proteins Membrane Proteins Ovarian Diseases

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References (43)

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