Disrupted trans-placental thyroid hormone transport in a human model for MCT8 deficiency

Abstract

Maternal-to-fetal transfer of the thyroid hormone T4 is essential for prenatal neurodevelopment, but the transporter facilitating trans-placental T4 transport is unknown. Mutations in the thyroid hormone transporter MCT8 cause a neurodevelopmental and metabolic disorder which key clinical features can be ameliorated by the T3 analogue TRIAC. The placenta has defective MCT8 if the fetus has MCT8 deficiency as the placenta is a fetal tissue. Should placental MCT8 be physiologically relevant, defective T4 transport across the placenta could represent a hitherto unrecognized mechanism underlying MCT8 deficiency. We investigated the importance of MCT8 and the trans-placental transport of TRIAC using an ex vivo human placental perfusion setup. Our study (i) showed that MCT8 has a major role in maternal-to-fetal T4 transport, (ii) implies that disrupted placental transport of thyroid hormones could be the culprit in the early cascade of events in MCT8 deficiency and (iii) indicated that the T3 analogue TRIAC is efficiently transported across the placenta, independent of MCT8, holding potential in mothers carrying fetuses with MCT8 deficiency.