Platelet-derived factors dysregulate placental sphingosine-1-phosphate receptor 2 in human trophoblasts


  • F. Lyssy
  • J. Guettler
  • B.A. Brugger
  • C. Stern
  • D. Forstner
  • O. Nonn
  • C. Fischer
  • F. Herse
  • S. Wernitznig
  • B. Hirschmugl
  • C. Wadsack
  • M. Gauster


  • Reproductive BioMedicine Online


  • Reprod Biomed Online 47 (2): 103215


  • RESEARCH QUESTION: Sphingosine-1-phosphate (S1P) is an essential and bioactive sphingolipid with various functions, which acts through five different G-protein coupled receptors (S1PR1-5). This study investigates the localisation of S1PR1-S1PR3 in the human placenta and analyses the influence of different flow rates, various oxygen concentrations and platelet-derived factors on the expression profile of S1PRs in trophoblasts. DESIGN: Expression dynamics of placental S1PR1-S1PR3 were determined in human first trimester (n=10), pre-term (n=9) and term (n=10) cases. Furthermore, we investigated the expression of these receptors in different primary cell types isolated from human placenta, verified the findings with publicly available single cell RNA-Seq data from first trimester and immunostaining of human first trimester and term placentas. Moreover, we tested whether the placental S1PR subtypes are dysregulated in differentiated BeWo cells under different flow rates, different oxygen concentrations or presence of platelet-derived factors. RESULTS: qPCR revealed that S1PR2 is the predominant placental S1PR in first trimester and vanishes towards term. All other S1P receptors increased from first trimester towards term. S1PR1 could be localised in endothelial cells, whereas S1PR2 and S1PR3 are predominantly found in villous trophoblasts. Furthermore, S1PR2 was found to be significantly downregulated in BeWo cells when co-incubated with platelet-derived factors. CONCLUSION: Our study suggests that the placental S1PR repertoire is differentially expressed across gestation. S1PR2 expression in villous trophoblasts is negatively influenced by platelet-derived factors, which could contribute to downregulation of placental S1PR2 over time of gestation as platelet presence and activation in the intervillous space increases from mid of first trimester onwards.