Regulation of iron absorption during infancy and iron transfer to milk during lactation

With the understanding that both iron deficiency and iron excess have negative consequences, the regulation of intestinal iron absorption becomes very crucial as there is no excretory pathway involved. A study conducted in human infants suggested developmental changes in the regulation of iron absorption, but little is known about the molecular mechanisms that regulate iron absorption during infancy. Further, the mechanisms of iron transfer from plasma into milk during lactation are unclear. Two intestinal iron transporters, divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1) were recently identified in adult animals and are critical for iron absorption. We demonstrated that both iron transporters were present in the duodenum of the 1-day-old rat pups, and were developmentally regulated, with expression dramatically increasing by day 40 after birth. Intestinal DMT1 and FPN1 gene expression did not change with either iron supplementation or iron deficiency at day 10 after birth. However, their expression decreased and increased significantly with iron supplementation and iron deficiency, respectively, by day 20, indicating developmental regulation of iron absorption. We also showed that both iron transporters were expressed in rat mammary gland, and their expression decreased throughout lactation, which correlated with the normal decline in milk iron throughout lactation. Milk iron of rats with low maternal iron status was not compromised, indicating regulation of milk iron transfer. Expression of the iron transporters was not changed by low maternal iron status; however, the presence of a smaller size DMT1 protein in the mammary gland of the low iron rats may be responsible for the increased iron efflux into milk. In summary, the current findings provide evidence for developmental regulation of iron absorption at a molecular level during infancy, and indicate a possible role for DMT1 and FPN1 in iron transport from the mammary gland to milk.