Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 38 P355 | DOI: 10.1530/endoabs.38.P355

SFEBES2015 Poster Presentations Reproduction (36 abstracts)

Vitamin D regulates extravillous trophoblast migration by inhibiting sphingosine-1-phosphate (S1P) signalling via S1P receptor 2

Edward Johnstone , Khiria Al-Saghir , Cherlyn Tan , Daman Adlam & Melissa Westwood


University of Manchester, Manchester, UK.


Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). Metabolomic profiling of placentas from such pregnancies has identified deranged sphingolipid metabolism as one of the pathways altered in PE. In other systems, the bioactive sphingolipid, sphingosine-1-phosphate (S1P) controls cell migration therefore this study aimed to determine its effect on extravillous trophoblast (EVT) function.

S1P (50 nM–10 μM) attenuated migration of the EVT cell lines, Swan-71 and SGHPL-4 (P<0.05). QPCR and immunolocalisation demonstrated that these cells express S1P receptors 1–3. However S1PR2 was responsible for mediating S1P’s inhibitory effect as the specific S1PR2 inhibitor, JTE-013 (100 nM) abolished S1P-attenuated migration (P<0.05) whereas treatment with the S1R1/3 inhibitor, FTY720 (100 nM), had no effect. S1PR2 can associate with the G proteins Gα12/13, Gαq, or Gαi, however analysis of Swan-71 cell migration and actin cytoskeleton in the presence of S1P±the Rho kinase inhibitor, Y-27632 (10 μM; n=6) suggests preferential activation of Gα12/13. Recent studies of osteoclast suggest that S1PR2 is regulated by vitamin D thus we investigated whether vitamin D affects S1P signalling in trophoblast. QPCR analysis revealed a significant reduction (fourfold decrease; P<0.05) in S1PR2, but not R1 and R3, expression after treatment with 10 mM 1,25(OH)2D3 for 48 or 72 h. Moreover, S1P did not inhibit the migration of Swan-71 cells exposed to 10 nM 1,25(OH)2D3 (P<0.05).

This study demonstrates that although EVT express three S1P receptor isoforms, S1P predominantly signals through S1PR2/Gα12/13 to activate Rho and actin stress fibre formation 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.

Volume 38

Society for Endocrinology BES 2015

Edinburgh, UK
02 Nov 2015 - 04 Nov 2015

Society for Endocrinology 

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