Iron metabolism during pregnancy is heavily biased towards maintaining the fetal supply, even at the extent of inducing severe anaemia in the mother. In this study we examined the effect of iron (Fe) deficiency and supplementation on the hierarchy of Fe supply and the gene expression of proteins involved in Fe metabolism. Female Hooded Lister rats were fed a control diet for 2 weeks following weaning, then a diet with control (50mg/kg) or deficient (7.5mg/kg) Fe content. Four weeks later, they were mated with males of the same strain. Following mating, the dams continued on the deficient diet or were given an Fe supplemented (150mg/kg) diet during either half of pregnancy. A control group were maintained on a normal Fe diet throughout the experiment. The dams were killed by exsanguination under terminal anaesthesia, at either day (D) 0.5, 12.5 or 21.5 of gestation and tissues and blood samples collected. Samples were also collected from fetuses, killed by Schedule 1 method, at D21.5. All animal procedures were conducted in accordance with the UK animals (Scientific Procedures) act. All data are expressed as mean ± s.e.m, n=8 per time point and treatment. Maternal liver Fe levels were already lower in deficient animals at the start of pregnancy, and never recovered, irrespective of treatment. Haematocrit (Hct; 39±0.5%) was maintained in control and deficient dams until D12.5 but dropped to 28.6±0.4% (p<0.05) in the deficient dams by D21.5. In the fetus, in contrast, fetal liver Fe was returned to normal (1.3±0.06 mg/g dry wt) by supplementation in the second half of pregnancy, and Hct (35±0.6%) followed the same pattern. The data show, therefore, that fetal Hct and liver stores are restored at the expense of both maternal Hct and liver stores. Placental transferrin receptor (TfR) expression was higher in deficient animals and in those supplemented in the first half of gestation only. As expected, levels correlated closely with fetal liver Fe levels (p<0.0001). The data suggest that hepcidin from the fetal liver mediates this signalling, since there is significant correlation between the two parameters (p<0.001). There was a linear relationship between maternal liver Fe levels, maternal liver TfR and hepcidin mRNA. However, there was a significantly greater interaction between them and fetal liver Fe. This was best described for TfR by a “broken stick” mode (p<0.001), with the break occurring at about 1.2mg/g dry wt. This is particularly exciting, since it suggests that the fetal liver is communicating Fe status to the maternal liver, and regulating metabolism through some, as yet unidentified, mechanism. In summary, the data show that the fetus has a remarkable capacity to accumulate Fe at the expense of the mother, and does so by manipulating Fe stores, haematocrit and the genes of Fe metabolism.Acknowledgements: This work is supported by SEERAD and the European Union.