During early pregnancy, the invasion of trophoblast cells into the decidua of the uterus is one of the essential steps in appropriate placentation. In this period, trophoblast cells are exposed to a relatively low-oxygen environment. The c-met proto-oncogene product (Met), which is a high-affinity receptor for hepatocyte growth factor (HGF), plays an important role in controlling the invasion of many types of cells. The present study was designed to investigate the effect of low-oxygen tension on Met expression and the invasiveness of trophoblast cells isolated from early-stage human placenta and trophoblast-derived BeWo cells and JEG-3 cells. RT-PCR and immunoblot analyses demonstrated that low-oxygen tension (1% O₂) stimulated the expression of Met mRNA and protein, respectively. HGF production in the cells was not affected by oxygen tension. Transient transfection of BeWo cells with a hypoxia-inducible factor (HIF)-1 expression vector to induce exogenous expression of HIF-1 significantly increased the level of Met mRNA and protein compared with transfection of a control vector. To examine whether this up-regulation of Met was directly induced by HIF-1, we performed the chromatin immunoprecipitation (ChIP) assay, which revealed that HIF-1 binds to the promoter region of the Met gene under low-oxygen tension. JEG-3 cells cultured under 1% O₂ showed a more invasive character than those cultured under 20% O₂, while inhibition of Met expression by small interfering RNAs (siRNAs) prevented the low-oxygen- tension-induced invasiveness. These results suggest that the induction of Met expression by low-oxygen tension may play an important role in the physiology of early pregnancy by promoting the invasion of trophoblast cells into the decidua of the uterus.