Background: Peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) is a transcriptional co-activator that drives mitochondrial biogenesis and other metabolic programs in many tissues, including the heart. PGC-1α is a powerful regulator of angiogenesis, a process of fundamental importance to the development of a healthy placenta in normal pregnancy. The angiogenic function of PGC-1α has been previously described in the heart where it has been shown to regulate angiogenesis. Its function and expression in the placenta is unknown. It may be the key link between placental development and the imbalance of key angiogenic factors observed in the pregnancy specific condition of pre-eclampsia. Hypothesis: PGC-1α is expressed in the human placenta and in pathophysiological conditions, such as pre-eclampsia, the expression of PGC-1α is reduced. Methods: Human placental samples were obtained from normal healthy pregnant women (n=4) for processing and analysed by means of immunohistochemistry using Calbiochem Anti PGC-1α, C-Terminal (777-797) rabbit polyclonal antibody. In addition, protein expression of PGC-1α was examined in placental tissue from normal pregnant rats (n=6) and those with surgically reduced uteroplacental perfusion (reduced uterine perfusion pressure (RUPP) model) (n=4). Results: Positive staining for PGC-1α was noted in both human and rat placental samples with varying degrees of expression when compared with PBS treated controls. Expression was most prominent in the endothelial cells surrounding the vessels, the trophoblasts, syncytiotrophoblasts and vascular endothelial cells with scattered staining in the maternal decidua and stroma. Furthermore, RUPP placental tissue indicated lower levels of positive staining for PGC-1α when compared with normal and sham rats. Conclusion: This study indicates that the transcriptional co-activator PGC-1α is expressed in the both human and rat placental tissue and is strongly localised to endothelial cells. Furthermore, our data may implicate PGC-1α in the pathogenesis of complications of pregnancy such as pre-eclampsia, but further investigation is needed to confirm this. Future studies could suggest the use of PGC-1α as a future pharmacological target for the treatment of complicated pregnancies.