The Influence of Gestational Age and Fetal Iron Status on Iron Regulatory Protein Activity and Iron Transporter Protein Expression in Third Trimester Human Placenta

Placental iron transport during the last trimester of pregnancy determines the iron endowment of the neonate. Iron transport is a function of the major iron transport proteins, transferrin receptor-1 (TfR-1) and ferroportin-1 (FPN-1). The mRNAs for TfR-1, and potentially FPN-1, are post-transcriptionally regulated by iron regulatory protein-1 (IRP-1) and -2 (IRP-2). We assessed the effect of gestational age and fetal iron status on IRP-1 and IRP-2 binding activity and on the localization and protein expression of TfR-1 and FPN-1 protein in 21 placentas from 24 to 40 weeks gestation obtained from iron-sufficient, nonanemic mothers. Gestational age had no effect on cord serum ferritin concentration, IRP-2 RNA-binding activity, transporter protein location, and TfR-1 or FPN-1 protein expression. IRP-1 activity remained constant until term, when it decreased (p=0.01). Placental ferritin expression (r=0.76; p<0.001) and FPN expression (r=0.44; p<0.05) increased with gestational age. Fetal iron status, as indexed by cord serum ferritin concentration, was inversely related to placental IRP-1 (r=-0.66; p<0.001) and IRP-2 activities (r=-0.42; p=0.05). Placental ferritin protein expression correlated better with IRP-1 activity (r=-0.45; p=0.04) than with IRP-2 activity (r=-0.35; p=0.10). Placental TfR-1 and FPN-1 protein expression were independent of fetal or placental iron status and IRP activities. Iron status had no effect on transport protein localization. We conclude that toward the end of the third trimester of iron-sufficient human pregnancy, the placenta accumulates ferritin and potentially increases placental-fetal iron delivery through increased FPN-1 expression. IRP-1 may have a more dominant role than IRP-2 activity in regulating ferritin expression.