Abstract: Objective · To investigate the effects and mechanisms of pregnancy immune tolerance induced by a novel immunosuppressive agent FTY720 and to provide experimental basis for the clinical treatment of unexplained recurrent spontaneous abortion.  Methods · The mice of spontaneous abortion model were used as subjects. The effects of intraperitoneal injection of FTY720 on the embryo loss rate in mice of spontaneous abortion model and on the expression of sphingosine-1-phosphate (S1P) in the decidual tissue were observed. S1P-siRNA lentiviral vectors and S1P-overexpression gene lentiviral vectors were constructed and transfected into dendritic cells (DCs) from mouse bone marrow. The effects of FTY720 on the embryo loss rate in mice of spontaneous abortion model after adoptive transferring of these two types of lentiviral vectors were observed.  Results · FTY720 had no significant effect on the embryo loss rate in normal pregnant mice. Intraperitoneal injection of FTY720 significantly reduced the embryo loss rate in mice of spontaneous abortion model. The expression of S1P in the decidual tissue in mice of spontaneous abortion model was low. After adoptive transferring of S1P-siRNA lentiviral vector transfected DCs, FTY720 could slightly reduce the embryo loss rate in mice of abortion mouse model, but the effect was far less than that of before adoptive transferring of S1P-siRNA lentivirus transfected DCs. After adoptive transferring of the S1P-overexpression gene lentiviral vector transfected DCs, FTY720 could significantly reduce the rate of embryo loss in mice of spontaneous abortion model and the effect was more significant than that of before adoptive transfecting of S1P-overexpression lentiviral vector transfected DCs.  Conclusion · FTY720 is safe. The induction of pregnancy immune tolerance may be related to the blockage of S1P signaling pathway.

Key words: sphingosine-1-phosphate signaling pathway, pregnancy immune tolerance, maternal-fetal interface, FTY720