Bisphosphoglycerate mutase (BPGM) is an enzyme expressed in erythrocytes. It catalyses the formation of 2,3 bisphosphoglycerate (2,3-BPG), which modulates oxygen transport by stabilizing the deoxygenated form of haemoglobin. Without 2,3-BPG, haemoglobin cannot function. Fetal haemoglobin is morphologically different to adult having almost no binding affinity to 2,3-BPG. Therefore if both fetal and adult haemoglobin are in the presence of 2,3-BPG, it will preferentially lower the oxygen affinity of adult haemoglobin. The fetal haemoglobin, being largely unbound to 2,3-BPG will retain a high affinity for oxygen taking up the oxygen released by the adult haemoglobin. Microarray experiments on placentae, utilising a mouse model of growth restriction highlighted BPGM as a key down-regulated molecule in growth restriction. We hypothesised that this down-regulation might be present in human growth restriction. We therefore examined pre-eclamptic pregnancies (at term), a disease strongly associated with growth restriction. We report that BPGM is expressed in, and localised to, the mouse labyrinthine trophoblast and human syncytiotrophoblast, as demonstrated by in situ localisation and immunohistochemical staining (Pritlove et al. 2005). Insulin-like growth factor II (IGF-II) plays a key role in cellular growth and is paternally expressed in the fetus and placenta. Pregnant Igf-2 knockout (KO) mice exhibit reduced placental growth and deliver growth-restricted pups as a result of insufficient nutrition during gestation (Constancia, 2002). Microarray data showed a 3-fold down-regulation of BPGM expression in the Igf-2 mouse placentae (heterozygote KO IGF-2 male vs. B6CBF1 female) when compared to wild type (n=3) which was confirmed using quantitative real-time PCR (TaqMAN, ABI systems). Real time PCR data also reported that BPGM expression was lower in placentas of 7 pre-eclamptic pregnancies compared to 7 normal (no clinical evidence of growth restriction) suggesting a correlation between low BPGM expression and growth restriction. The physiological relevance of this was investigated by measuring maternal circulating 2,3-BPG during gestation in both IGF2 KO and WT mice (n=6 at three time points). A statistically significant reduction was noted at E11 and at E15 (p<0.05). No difference was noted at E18. We are uncertain as to whether the decreased levels of BPGM seen in both dysfunctional mouse and human pregnancy represent a cause or effect of growth restriction. These results, however, do raise the intriguing possibility that measurement of circulating 2,3-BPG in human pregnancy might also alter in a pattern that would allow identification of IUGR well before clinical symptoms manifest.