Hepcidin, a small peptide synthesised in liver, regulates iron homeostasis by inhibiting intestinal Fe absorption, iron recycling by macrophages and the release of Fe from stores. Hepcidin reduces the expression of Divalent Metal Iron Transporter 1 (DMT1) necessary for intestinal Fe uptake, and inhibits cellular Fe efflux by binding and inducing the degradation of the Fe exporter Ireg1. Duodenal Fe absorption increases during pregnancy to compensate for the increasing requirements of the placenta and fetus. An inverse relationship between hepcidin and intestinal Fe transporters during pregnancy has been demonstrated by Millard et al. (2004). Placental Fe transfer also increases during pregnancy; however, the relationship between maternal hepcidin expression and placental Fe transfer has yet to be established. The aim of this study was twofold. Firstly, to determine the relationship between hepcidin expression and duodenal and placental DMT1 and Ireg1 at different stages of pregnancy and secondly, to determine the effect of hepcidin on Fe uptake in BeWo cells (an in vitro model for syncytiotrophoblasts). mRNA levels of Fe transporters were quantified by real-time PCR in post mortem tissue from pregnant Wistar rats during the 2nd (day 14-15) or the 3rd (day 19-21) trimester (n=6). Changes in mRNA levels were not evident during the 2nd trimester (Table 1). However hepcidin expression was significantly reduced in the 3rd trimester when the expression of duodenal and placental DMT1 was increased. In the second study BeWo cells were incubated with synthetic hepcidin (10-100µM) for 24h. Cells were then taken to measure Fe uptake from Fe59-Tf and expression of DMT1 and Ireg1 was quantified by real-time PCR. Iron uptake was reduced in cells exposed to hepcidin. This reduction was dose dependent (0µM treatment: 530.82±20.57; 10µM: 183.17±38.58; 100µM: 125.63±28.12 µmol Fe uptake/g/min, n=3, P<0.001). Cells incubated with hepcidin also had decreased DMT1 (0µM: 1.00±0.05; 1µM: 0.41±0.05; 10µM: 0.48±0.20; 100µM: 0.57±0.02, P<0.05) and Ireg1 (0µM: 1.00±0.05; 1µM: 0.46±0.16; 10µM: 0.70±0.06; 100µM: 0.77±0.04, P<0.05) expression. These data demonstrate that the gestational increase in placental and duodenal iron transporters is linked with a decrease in hepcidin expression. In addition we demonstrate that in vitro hepcidin can regulate placental iron absorption by reducing the uptake of transferrin bound Fe and probably Fe efflux (not determined in this study). This reduction is linked with decreased expression of DMT1 and Ireg1. All data are presented as mean±SEM. Differences between groups were calculated by ANOVA or Kruskal-Wallis.