Role of the placenta in regulation of fetal iron status

Abstract

During pregnancy, the developing fetus is entirely dependent on its mother for nutrition and waste disposal, which take place almost exclusively across the placenta. The placenta is, however, not just a passive mediator; it can also regulate the rates and amounts of nutrient transported. This is particularly true for iron transport. This review examines how the fetus, and not the mother, regulates iron uptake and transfer across the placenta, how these processes interact, and how the fetus can modulate iron metabolism in the mother.

ZIP8 Is an Iron and Zinc Transporter Whose Cell-surface Expression Is Up-regulated by Cellular Iron Loading

“…Strong ZIP8 expression in placenta was also noted in a previous study in which placental ZIP8 expression was second highest out of 16 human tissues after pancreas (and even more abundant than in lung) (18). It is unknown how iron is transported across the placenta to the developing fetus (50). We do know, however, that DMT1 and ZIP14 are not required for maternofetal iron transfer because Dmt1 and Zip14 (Slc39a14) knock-out mice are born alive with adequate amounts of iron (1,51).…”

Prenatal Iron Supplementation Reduces Maternal Anemia, Iron Deficiency, and Iron Deficiency Anemia in a Randomized Clinical Trial in Rural China, but Iron Deficiency Remains Widespread in Mothers and Neonates

“…Maternal iron status has been shown to influence iron transfer to the fetus late in pregnancy by using stable isotopes (32), but fetus and placenta also play a role. Placental iron transport is upregulated as fetal iron status becomes compromised (33,34), resulting in more iron transfer to the fetus. This is at the expense of the mother if external sources of iron are inadequate to meet iron needs.…”

Placental heme receptor LRP1 correlates with the heme exporter FLVCR1 and neonatal iron status

“…The high Fe transport capacity of the placenta is partly explained by the abundant presence of TfR on the syncytiotrophoblast (Loh et al 1980) and it is believed that transferrin-bound inorganic Fe is the predominant form of Fe utilized by the placenta to support fetal requirements (van Dijk 1988, McArdle et al 2011). Recently, attention has been focused on the presence of multiple heme transport proteins in the human placenta (Cao & O’Brien 2013), which suggests that this organ may be an alternate site of heme clearance and/or utilization.…”