Vitamin D attenuates sphingosine-1-phosphate (S1P)-mediated inhibition of extravillous trophoblast migration. (December 2017)

• Record Type: Journal Article
• Authors: Westwood, Melissa; Al-Saghir, Khiria; Finn-Sell, Sarah; Tan, Cherlyn; Cowley, Elizabeth; Berneau, Stéphane; Adlam, Daman; Johnstone, Edward D.
• Is Part Of: Placenta. Volume 60(2017:Dec.)
• Page Start: 1
• Page End: 8
• Publication Date: 2017-12
• Subjects: S1P -- Vitamin D -- GPCR -- Trophoblast -- Migration -- Lipid signalling -- Placenta -- Pre-eclampsia; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2017.09.009
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). In other systems, the sphingolipid, sphingosine-1-phosphate (S1P), controls cell migration therefore this study determined its effect on extravillous trophoblast (EVT) function. Methods: A transwell migration system was used to assess the behaviour of three trophoblast cell lines, Swan-71, SGHPL-4, and JEG3, and primary human trophoblasts in the presence or absence of S1P, S1P pathway inhibitors and 1, 25(OH)2 D3 . QPCR and immunolocalisation were used to demonstrate EVT S1P receptor expression. Results: EVTs express S1P receptors 1, 2 and 3. S1P inhibited EVT migration. This effect was abolished in the presence of the specific S1PR2 inhibitor, JTE-013 (p < 0.05 versus S1P alone) whereas treatment with the S1R1/3 inhibitor, FTY720, had no effect. In other cell types S1PR2 is regulated by vitamin D; here we found that treatment with 1, 25(OH)2 D3 for 48 or 72 h reduces S1PR2 (4-fold; <0.05), but not R1 and R3, expression. Moreover, S1P did not inhibit the migration of cells exposed to 1, 25(OH)2 D3 (p < 0.05). Discussion: This study demonstrates that although EVT express three S1P receptor isoforms, S1P predominantly signals through S1PR2/Gα12/13 to activate Rho and thereby acts as potent inhibitor of EVT migration. Importantly, expression of S1PR2, and therefore S1P function, can be down-regulated by vitamin D. Our data suggest that vitamin D deficiency, which is known to be associated with PE, may contribute to the impaired trophoblast migration that underlies this condition. Highlights: Sphingosine-1-Phosphate (S1P) controls extravillous trophoblast (EVT) migration. Control of migration is exerted through Sphingosine-1-Phosphate receptor 2 (S1PR2). Vitamin D attenuates the expression of S1PR2 and therefore promotes EVT migration in the presence of S1P.