Patel J.,University of Queensland |
Patel J.,Bancroft Center |
Landers K.A.,Bancroft Center |
Mortimer R.H.,University of Queensland |
And 3 more authors.
Journal of Endocrinology | Year: 2012
Transplacental delivery of maternal thyroid hormones to the fetus, in particular thyroxine (T 4), is critical in ensuring normal fetal neurological development. The fetus relies on maternal T 4 till around 16 weeks gestation, but mechanisms of placental T 4 transport are not yet fully elucidated. Placenta produces, secretes and takes up the thyroid hormone-binding protein transthyretin (TTR). Many placental genes are regulated by oxygen levels, which are relatively low (1%) in the early first trimester, rising to 3% in the mid first trimester and 8% in the early second trimester and thereafter. We examined the expression and uptake of TTR in isolated primary human placental cytotrophoblast cells cultured under different oxygen concentrations (1, 3, 8, 21% O 2 and 200 mM desferrioxamine (DFO)) for 24 h. We observed sevenfold higher expression of TTR mRNA and protein levels at 1% O 2 than at 8 and 21% O 2. Significant increases were observed after culture at 3% O 2 and following DFO treatment. We observed significantly higher uptake of 125I-TTR and Alexa-594-TTR when cells were cultured at 1 and 3% O 2 and in the presence of 200 μM DFO than at 8 and 21% O 2. When JEG-3 choriocarcinoma cells were transfected with TTR promoter reporter constructs, increased luciferase activity was measured in cells cultured at 1 and 3% O 2 in comparison to 8 and 21% O 2.We conclude that placental TTR expression and uptake is increased by the relative hypoxia observed in the first trimester of pregnancy, a time when materno-fetal T 4 transfer is the sole source of fetal T 4. © 2012 Society for Endocrinology.