4.7 Article

Sphingosine pathway deregulation in endometriotic tissues

期刊

FERTILITY AND STERILITY
卷 97, 期 4, 页码 904-U312

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ELSEVIER SCIENCE INC
DOI: 10.1016/j.fertnstert.2011.12.051

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Endometriosis; sphingosine pathway; sphingosine-1-phosphate; S1P; apoptosis

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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. (Fertil Steril (R) 2012;97:904-11. (C)2012 by American Society for Reproductive Medicine.)

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