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The effect of axon guidance factors ephrin-A 1/EphA2 on the invasion of trophoblastic cells and the possible mechanism were investigated in this study.The expression of EphA2 in vascular endothelial cells was detected by immunohistochemistry.The proliferation and invasion of TEV-1 cells (an extravillous trophoblastic cell line) in first trimester were determined by cell counting kit-8 (CCK-8)and Transwell invasion assay.Real-time PCR was used to detect the expression of ephrin-A1 in TEV-1cells treated with EphA2 at different concentrations (10,50,100,500,1000 and 5000 μg/L).The results showed:(1) EphA2 was expressed in the vascular endothelial cells; (2) EphA2 could promote the proliferation of TEV-1 cells.The proliferative capacity reached a peak in TEV-1 cells treated with 100 μg/L EphA2 (P＜0.05); (3) EphA2 could increase the invasion of TEV-1 cells.The invasive ability was the greatest in TEV-1 cells treated with 500 μg/L EphA2 (P＜0.05); (4) in the presence of EphA2 (0-500μg/L),the expression of ephrin-A1 was increased concentration-dependently (P＜0.05),but when the concentration of EphA2 was over 500 μg/L,the expression of ephrin-A 1 ceased to increase (P＞0.05).It was concluded that EphA2 can promote the invasion and proliferation of the human extravillous trophoblastic cells probably by regulating the ephrin-A1 ligand.