BACKGROUND AND AIMS: HFE functions as an upstream regulator of liver hepcidin which has been demonstrated to be a negative regulator of intestinal dietary iron absorption and efflux of recycled iron from macrophages. Hepcidin has also been proposed to be a negative regulator of iron efflux from placenta, however it is not known if this of maternal or foetal origin. Furthermore, HFE has been demonstrated to be present in the placenta, but its role in the dynamics of maternal foetal in iron transfer independent of hepcidin is unknown. In this study we investigated the effects of HFE and dietary iron levels on transfer of iron from mother to foetus in order to determine the importance of maternal and foetal HFE status on iron transfer. MATERIALS AND METHODS: HFE knockout (KO), wild type (WT), and heterozygote (HET) dams were fed 50 and 200ppm iron diets and mated with HET male mice to produce pups of all genotypes. Dams and pups were sacrificed and pup liver iron levels were determined. mRNA levels of iron transporter genes (Ferroportin1, TfR1, DMT1+IRE, and DMT1-IRE) were determined in placental tissue by real-time PCR. RESULTS: Liver iron levels of HET pups from KO dams fed 50ppm iron diet were considerably higher (137.42 + 9.19 µg/g dry weight, n = 10) than those from WT dams (112.90 + 3.71 µg/g dryweight, n = 10). This difference was also apparent in the pup liver iron levels when the dams were fed 200ppm iron diet. Iron transporter gene expression was higher in HET pups from KO dams compared to those from WT dams fed 50ppm iron diet but this difference was not significant in HET pups from dams fed 200ppm iron diet. There was no difference in liver iron levels of KO (115.9 + 7.09 µg/g dryweight, n = 10) and WT pups (113.47 + 3.61 µg/g dry weight, n = 10) from HET dams fed 50ppm iron diet. This was mirrored in the gene expression data, which showed no significant difference between all of the placental genes tested (see above). However liver iron levels of KO and WT pups from HET dams fed 200ppm iron diet were higher in KO pups (146.95 + 9.34 µg/g dryweight, n = 10) than WT (122.08 + 4.74 µg/g dryweight, n = 10). In addition, expression of placental iron transporter genes was also found to be significantly elevated in KO pups than WT. CONCLUSIONS: Maternal genotype plays a role in regulating placental iron transfer independent of dietary iron content. However, foetal genotype seems to affect liver iron accumulation and the expression of certain iron transporter genes only with adequate iron intake.