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.
Fertil Steril. 2012 Apr;97(4):904-11. doi: 10.1016/j.fertnstert.2011.12.051. Epub 2012 Jan 24.
To investigate key genes expression of the sphingosine-1-phosphate pathway in endometriotic tissues.
A case-control laboratory study.
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.
研究鞘氨醇-1-磷酸通路相关基因在子宫内膜异位症组织中的表达。
病例对照实验室研究。
三级甲等大学医院。
共 31 名女性参与了研究，其中 16 名患有子宫内膜异位症（病例组），15 名不患有子宫内膜异位症（对照组）。
在经过手术切除和病理分析后，从患有和不患有子宫内膜异位症的女性中获取子宫内膜组织样本。
通过实时定量聚合酶链反应（PCR）检测 15 名无疾病女性、16 名病例组患者的在位和异位子宫内膜中 SPHK1-2、SGPP1-2、SGPL1、SPHKAP 和 S1PR1-5 的信使 RNA 表达，进一步通过免疫组化检测 S1PR1 和 S1PR2 的表达。
SGPP2 在子宫内膜异位症患者的在位和异位内膜中表达下调（分别为 1.7 倍和 16.7 倍）。SGPP1 在健康子宫内膜中弱表达，在子宫内膜异位症患者中上调（分别为 11.9 倍和 64.7 倍），但表达水平仍较低。SGPL1 在异位内膜中表达下调（3.3 倍），SPHKAP 在异位内膜中表达上调（112.6 倍），与无疾病女性的子宫内膜相比。在子宫内膜异位症患者中，S1PR3 在在位和异位内膜中表达下调（分别为 2.1 倍和 6.3 倍）；S1PR2 和 S1PR1 在在位和异位内膜中表达上调（分别为 2.5 倍和 2.6 倍）。这些变化在蛋白质水平上通过免疫组化得到了进一步证实。
在子宫内膜异位症病变中，参与调节鞘氨醇-1-磷酸水平平衡及其受体的酶的表达总体上严重失调，有利于鞘氨醇-1-磷酸的代谢减少。我们的研究结果表明，鞘氨醇途径在子宫内膜异位症病变的建立和存活中发挥作用。
