Normal placental development is essential for successful pregnancy. Critical to normal placental development is the invasion of cytotrophoblasts into the uterine wall and arterial remodeling. Defective trophoblast invasion can lead to poor placentation, prevents adequate establishment of blood supply in the first few months of pregnancy, limits uteroplacental perfusion and results in the later occurrence of pre-eclampsia (PE). PE affects ~3-10% of pregnancies and is characterised by clinical symptoms of hypertension and proteinuria. Elevated levels of thromboxane A2 (TXA₂) and isoprostanes (both ligands for the TXA₂ receptor) are readily detectable in pregnant women affected by PE. Our data suggests that there is differential expression of the human-specific TPβ isoform in PE, which would amplify the adverse effects of isoprostanes. We therefore determined whether TP isoforms differentially may potentially regulate the trophoblast function during placentation. The overexpression of TPα and TPβ in trophoblast cell lines, BeWo and JEG-3, significantly impacted cellular function. TPα overexpression enhanced forskolin-induced syncytialisation of BeWo cells and normal migration of JEG-3 cells. By comparison, ectopic expression of TPβ attenuated forskolin-induced syncytialisation and proliferation of BeWo cells and inhibited migration of JEG-3 cells. These effects were mediated through highly specific signalling pathways, independent of G-protein coupling of the receptor and largely due to direct protein-protein interactions of the unique intracellular tail of TPβ. These data suggest that the TPα isoform, expressed normally on trophoblasts, enhances the processes in trophoblasts required for normal placentation. However, the TPβ isoform produces a cellular phenotype that is consistent with the abnormal placentation observed in PE and indicates that the pathologic upregulation of TPβ in the placenta may play a role in regulating the onset and severity of PE.