Asymmetrical Transport of Thyroxine Across Human Term Placenta

Abstract

Background Fetal development is crucially dependent on thyroid hormone (TH). Maternal-to-fetal transfer of TH is a prerequisite for fetal TH availability, particularly in the first half of pregnancy. The mechanisms of trans-placental transport of TH, however, are yet poorly understood. We therefore investigated the TH transport processes across human placentas using an ex vivo perfusion system. Methods Intact cotyledons from term placentas of uncomplicated pregnancies were cannulated within 30 minutes after delivery and the maternal and fetal circulations were re-established. One hundred nM thyroxine (T4) was added to either the maternal or fetal circulation and perfusions run up to 3 hours during which samples were taken from both circulations at different time points. Variables included addition of iopanoic acid (IOP) to block activity of the deiodinase type 3 (D3) and bovine serum albumin (BSA) to trap released T4. T4 and 3,3’,5’-triiodothyronine (rT3) concentrations in the perfusates were measured by radioimmunoassays. Results Maternal-to-fetal transfer was slow, with T4 barely detectable in the fetal circulation unless D3 was blocked by IOP. Fetal T4 was detected after 3h-perfusion (10.6±0.6 nM) when BSA (34g/l) was added in the fetal circulation to trap the released T4. In contrast, fetal-to-maternal transfer of T4 was rapid and maternal T4 increased to 43.6±5.5 nM. Conclusions Materal-to-fetal T4 transport is limited whereas fetal-to-maternal is rapid indicating that T4 transport across human term placenta is an asymmetrical process. With the high D3 activity, our observations are compatible with a protective role of the placental barrier. Future studies should reveal how the placenta exerts its gatekeeper function in ensuring optimal TH passage to the fetus.