Placental development requires trophoblast cells to proliferate and invade maternal uterine tissues to establish utero-placental blood flow. This is critical for normal intrauterine development. The placental renin-angiotensin system (RAS) is involved in placentation particularly during the early post-implantation period, when trophoblast cells are at their most invasive. Binding of inactive prorenin to the (pro)renin receptor ((P)RR) can initiate the generation of angiotensin II (Ang II) via the classical RAS pathway. Ang II can act on the angiotensin type 1 receptor (AT1R) to stimulate placental angiogenesis and trophoblast invasion. However, the prorenin/(P)RR interaction and its functional role in placental development is unknown. We hypothesised that prorenin acting via (P)RR is a key regulator of placental morphogenesis. In our preliminary experiments in a first trimester human trophoblast cell line (HTR-8/SVneo) we knocked down (P)RR expression. HTR-8/SVneo cells were transfected with three different (P)RR siRNAs. (P)RR mRNA expression was determined via qPCR. All three siRNAs significantly decreased (P)RR mRNA expression when compared to both scrambled and non-transfected controls (P<0.0001). Cell viability (resazurin assay) after transfection with both scrambled and siRNA (P)RR knockdown was significantly enhanced compared with control (P<0.05) but there was no difference between the scrambled and intact siRNA treated cells. Although, overall the addition of VTP-27999 (renin inhibitor) was associated with a decrease in cell viability (P<0.05), there was no dose dependent effect. Treatment with another renin inhibitor (Aliskerin) and handle region peptide (HRP, which directly binds to prorenin) had no overall effect on cell viability. These experiments were carried out in 20% O2. Placentation occurs in low O2 milieu which we have shown alters the expression of the placental RAS. Therefore, although our preliminary experiments have shown minimal effects of (P)RR knockdown and renin inhibitors on cell viability, their effects may be amplified when repeated in a low O2 environment.