Fetal thyroid hormone synthesis and secretion begins around the 16th week of pregnancy and is dependent on placental transport of maternal iodide. Uptake of maternal iodide is regulated by the sodium iodide symporter (NIS) in the apical membrane of trophoblasts. NIS mRNA and protein are barely detectable in placental cells cultured in a hypoxic (1% O2) environment similar to that of early first trimester placenta. In cells cultured at 8% oxygen (similar to second trimester placenta) NIS mRNA and protein are significantly increased. We hypothesized that, during early pregnancy, placental NIS expression would be low and would increase with increasing placental vascularization in the second trimester, when the fetus requires iodide for thyroid hormone synthesis. We collected placentas from surgically terminated pregnancies between 6 and 17 weeks gestation and from normal term pregnancies following caesarean section and studied the ontogeny of NIS mRNA expression and protein levels.
From 6 to 12 weeks, NIS mRNA expression was strongly correlated with gestational age (r = 0.6, p < 0.0005). Thereafter NIS mRNA levels dropped rapidly until 14 weeks and remained low. NIS mRNA levels were also relatively low at term. NIS protein levels were very low at 6 weeks gestation but increased with increasing gestational age. Analysis of NIS protein levels from 6 to 12 weeks confirmed a linear relationship between gestation age and NIS protein levels (r = 0.34, p < 0.05). NIS levels were stable and not significantly correlated with gestational age between 12 and 17 weeks gestation (r = 0.12).
In conclusion, placental NIS protein levels are significantly correlated with gestational age during early pregnancy. This would lead to increased iodide supply to meet increased fetal requirements for thyroid hormone synthesis as the pregnancy progresses.