Molecular mechanism of regulation of iron transport across placenta

摘要

During the third trimester of pregnancy, iron transport from mother to theudfoetus against a concentration gradient determines the iron endowment inudfoetal and neonatal life. Hfe functions as an upstream regulator of liverudhepcidin which has been demonstrated to be a negative regulator of intestinaludabsorption of dietary iron and macrophage efflux of recycled iron. Hepcidinudhas also been proposed to be a negative regulator of iron efflux from theudplacenta, however it is not known if hepcidin is of maternal or foetal originudduring pregnancy. The exact mechanism and molecules involved in theudregulation of iron transport across the placenta are not well understood.udIn this study the effects of Hfe and dietary iron levels on transfer of iron fromudmother to foetus was investigated in order to determine the importance ofudmaternal and foetal Hfe status on iron transport. The effect of maternaludhepcidin on placental iron transport in WT and Hfe KO dams was also studied.udThe molecular mechanism of iron transport across placenta was elucidated byudusing BeWo cells as a model for iron uptake, transport and efflux.udThis study has shown that the mechanism regulating iron metabolism duringudpregnancy is dependent on the iron status of the mother and its genotype. Audclear link could be seen between the maternal iron status and foetal body ironudstores. The lack of Hfe in both dams and pups increased iron absorption in theudbody and raised serum iron levels but the effect of Hfe was diet dependent. However, foetal genotype seems to affect liver iron accumulation and certainudiron transporter gene expression only with low and normal iron diets.udIn this study BeWo cells were utilised to model the placentaludsyncytiotrophoblasts. The insensitivity of iron transporter proteins in BeWoudcells to hepcidin treatment might be due to the cell-specific response ofudhepcidin. TfR1, DMT1 and FPN1 were localised in these cells to understandudthe molecular mechanism of iron transport across placenta. Finally, theudpresence of ZIP14 and its response to hepcidin treatment in mice mayudindicate the presence of an alternative pathway of iron transport acrossudplacenta.