Solanky, Nita Shantilal;
(2005)
The molecular mechanisms of duodenal and placental iron absorption during pregnancy.
Doctoral thesis , UCL (University College London).
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Abstract
During pregnancy duodenal iron absorption, placental transfer, and the release of iron from stores in the mothers liver, are increased to meet the requirements of the developing foetus. The regulatory mechanisms co-ordinating these events are for the first time illustrated here. Various proteins, notably hepcidin and hfe, have been implicated as having a role in iron homeostasis. By quantitating the expression of hepcidin and the duodenal iron transporters: DMT1, Tfr1, Dcytb and Ireg1, in mice raised on iron-deficient and iron-loaded diets, this study confirms that hepcidin expression is positively regulated by body iron status and negatively regulates duodenal DMTI. A parallel study in hfe knockout mice, demonstrates inappropriately low hepcidin expression and elevated duodenal DMT1 levels. This provides a possible explanation for the liver iron loading characteristic of hereditary haemochromatosis. The expression of hepcidin is studied in pregnant rats and is shown to decrease during the final trimester when duodenal and placental iron transfer is maximal. This decrease is preceded by a reduction in liver iron stores and subsequent reduction in hepcidin expression. Iron supplementation to pregnant dams, increases liver iron status and hepcidin expression, this corresponds with a decrease in duodenal and placental DMT1 expression, whilst iron deficiency during this period, increases both duodenal and placental uptake. This implies that the increase in duodenal iron absorption observed during pregnancy is, at least in part, a consequence of reduced liver iron stores. Using an in vitro model of the placental syncytiotrophoblast, DMT1 is localised to endosomal compartments, but not co-localised with either Tfr1 or Ireg1. Hepcidin is demonstrated to bind to the plasma membrane of these cells and reduce the uptake of diferric-transferrin. These results provide new insight into the molecular processes of iron homeostasis and implicate a regulatory role for hepcidin, not only in duodenal, but also in placental iron uptake.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | The molecular mechanisms of duodenal and placental iron absorption during pregnancy |
| Identifier: | PQ ETD:602404 |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. Third party copyright material has been removed from the ethesis. Images identifying individuals have been redacted or partially redacted to protect their identity. |
| UCL classification: | |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1446479 |
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