Oxygen concentration regulates expression and uptake of transthyretin, a thyroxine binding protein, in JEG-3 choriocarcinoma cells

Maternal thyroid hormone is provided to the fetus before the onset of fetal thyroid function (at about 16 weeks) and is essential for normal neurologic development. Mechanisms of transport are uncertain but transthyretin (TTR), a thyroxine binding protein produced by the placenta may be involved. Placental oxygen concentrations in early pregnancy are low, about 1% early in the first trimester and rising to 8% over the next 12 weeks. This study investigated the regulation of TTR expression, secretion and uptake in JEG-3 placental cells cultured at different oxygen concentrations. TTR mRNA and protein expression and 125I-TTR and Alexa-Fluor594-TTR uptake were significantly higher in cells cultured at 1% and 3% O2, than at 8% O2. This suggests that increased carrier mediated T4 transport by placental TTR may be induced by the low oxygen environment of early pregnancy, a time when the fetus has its highest requirement for transport of maternal T4.