ABSTRACT
Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, has various functions to affect many signalling pathways leading to cellular proliferation and differentiation and to regulate of cell migration, invasion, and angiogenesis. However, there are little reports about the relation between trophoblast stem cells and S1P. Thus, the physiologic effects of S1P on trophoblast stem (TS) cells were investigated in this study. S1P was involved in early stage development of trophoblast via upregulation of Eomesodermine mRNA expression and suppressed differentiation of TS cells through activation of extracellular-signal regulated kinase (ERK) activation. Other actions of S1P were the activation of p38 and the induction of Dlx-3 mRNA expression for angiogenesis in TS cells. Interestingly, TS cells cultured with S1P for 4 days in thrombin-fibrinogen gel culture system, specific culture system for endothelial cells, showed good healthy appearance, but TS cells cultured without S1P got severe damages. Taken together, we suggest that S1P has very important roles on placenta such as development of early stage trophoblast, suppression of differentiation, and angiogenesis on placenta.