Normal fetal brain development is unquestionably dependent on an adequate regulated supply of thyroid hormone. Fetal hypothyroidism from environmental iodine deficiency has been recognised for centuries and remains 'the world's most prevalent – yet easily preventable – cause of brain damage' (www.who.int). Although severe iodine deficiency does not occur in Australia a recent Australia-wide collaborative study (involving members of our group and others) suggests that up to 40% of Australian schoolchildren may be iodine deficient, particularly in New South Wales and Victoria. Pregnant Australian women and their babies are therefore at risk of impaired thyroid function. Disturbingly, there is mounting evidence that low or even mildly reduced maternal thyroid hormone levels in the first trimester are associated with impaired intellectual development in the offspring.
Iodide transport through the placenta, from mother to fetus, is necessary for fetal thyroid hormone synthesis, which in turn is critical for normal fetal growth and development. However, the mechanism and regulation of iodide transport in placenta is poorly understood. To date at least two iodide transporters have been found, sodium/iodide symporter (NIS) and pendrin. Both transporters previously demonstrated in thyroid are also found in human placenta. This finding supports active iodide transport in placenta. Recently, using the BeWo human choriocarcinoma cell line as a placental model, we described an iodide transport system in placenta with similar affinity and specificity to thyroidal iodide accumulation. Confocal microscopy indicates that NIS is distributed to the apical (maternal) pole of the cells, consistent with functional studies in bicameral chambers, thus confirming the role of NIS in transplacental iodide influx. Additionally, we found evidence to suggest that pendrin is a major route for efflux of iodide from the trophoblast.
We have more recently found that the placenta regulates iodide transport differently depending upon the amount of iodide that is available (Li et al. 2007). When exposed to excessive iodide, the placenta decreases iodide uptake by producing less of its transporter (sodium-iodide symporter, NIS ) and when exposed to low concentrations of iodide, the placenta makes more NIS to maximise uptake. This mechanism will allow the placenta to protect the developing fetus from the toxic effects of excess iodide but also will maintain adequate amounts of iodide to reach the fetus during maternal dietary iodide deficiency. Additionally, we have found that high levels of iodide turn down production of the pregnancy hormone, human chorionic gonadotrophin (hCG). Adequately high levels of hCG are required to maintain pregnancy. We are currently investigating the regulation and pathways involved.
