Iron supplementation during infancy - effects on expression of iron transporters, iron absorption, and iron utilization in rat pups

Background: Studies conducted in human infants suggest developmental changes in the regulation of iron absorption; however, little is known about the molecular mechanisms regulating iron absorption during infancy. Two intestinal iron transporters, divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1), were recently identified. Objective: The objective was to investigate at a molecular level the regulation of iron absorption during infancy in a rat pup model. We examined the developmental expression of DMT1 and FPN1 and the effects of iron supplementation on their expression and on iron absorption and utilization during infancy. Design: Rat pups were given daily oral doses of 0, 30, or 150 mug Fe from day 2 to day 20 after birth. On days 10 and 20 after birth, Fe-59 absorption, tissue minerals, and intestinal DMT1, FPN1, and ferritin expression were examined. To assess developmental expression, DMT1 and FPN1 were examined in control rats from days I to 50 after birth. Results: Intestinal DMT1 and FPN1 were significantly affected by age; expression increased dramatically by day 40. On day 10, no significant effect of iron supplementation on DMT1 and FPN1 gene expression or on iron absorption was observed. By day 20, DMT1 and FPN1 expression and iron absorption had decreased significantly with iron supplementation. Conclusions: During early infancy, rat pups are unable to down-regulate intestinal iron transporters or iron absorption in response to iron supplementation, whereas down-regulation occurs during late infancy. The current findings provide evidence of the developmental regulation of iron absorption, which emphasizes the need for caution when giving iron supplements to infants at an early age.