Iron transporters in the human mammary gland and their relationship to low iron concentrations in human milk
Extremely low iron content in human milk has been documented, yet whether the iron in breastmilk is adequate for exclusively breastfed infants and the underlying mechanism responsible for low iron in human milk are still unclarified. Evidence from current meta-analysis suggests that iron supplementation to health exclusively breastfed infants improve their iron status and cognitive development, but may delay their physical growth. There was no evidence to suggest iron supplementation could cause other adverse effects. In order to address why iron is low in human milk, human breast milk samples from nine lactating women were used to investigate the gene expression profiles of iron transporters and iron-binding proteins in the milk fat. The mRNA extracted from breast milk fat globules was confirmed mainly from epithelial cells. The expression of transferrin receptor 1(TFRC), divalent metal transporter 1 (SLC11A2), transferrin (TF) and lactoferrin (LTF) were detected. Remarkably, the iron transmembrane release protein FPN was absent, which is in contrast to data confirming its presence in the rat mammary glands from the previous study. Furthermore, a comparative analysis of the iron transporters expressed in the RNA extracted from human milk fat and milk cells was conducted. Human milk samples were collected from fifteen eligible lactating women. It was found that the RNA in human milk fat is from epithelial cells, while the RNA in human milk cells originated from both epithelial cells and leukocytes. The expression of TFRC, TFR2, SLC11A2, TF and LTF was confirmed in the RNA isolated from both the milk fat and the milk cells. Two other transporters, SLC11A1 and SLC40A1, were only found in the RNA isolated from milk cells. Overall, this study’s findings suggest that RNA from milk fat and milk cells could be used as a novel tool to investigate the biological functions of lactating epithelial cells and lactating mammary glands, respectively, by different purposes. The lack of iron exporter in lactating epithelial cells suggests that a novel iron transport routine may be used during human lactation.