The placenta in fetal thyroid hormone delivery: from normal physiology to adaptive mechanisms in complicated pregnancies

Context: Thyroid hormones are indispensable for normal fetal development. Since the fetus depends to a large extent on maternal thyroid hormone supply through the placenta, this challenges maternal thyroid economy. Several molecular mechanisms are involved in placental thyroid hormone transport and metabolism. Chronic pregnancy complications, associated with utero-placental hypoxia, trigger the development of accelerated placental maturation in order to improve fetal-placental exchange to strengthen the offspring's chance of survival. This review provides an overview of normal maternal-fetal thyroid hormone supply and explores the presence of placental adaptive mechanisms in complicated pregnancies with chronical utero-placental hypoxia to improve the thyroid hormone supply to the fetus under pressure, to end with reflections about the long term health consequences.Evidence acquisition: This work is based on a comprehensive literature review of the PubMed and Embase database, including relevant articles from 1969 to June 2018.Conclusions: The placenta is actively involved in fetal thyroid hormone delivery through a combination of stimulatory and inhibitory mechanisms. Parallel with histological adaptations to improve transplacental fetal-maternal exchange, there are indications of placental adaptive mechanisms in thyroid hormone transport and metabolism in case of complicated pregnancies, from animal models and in-vitro experiments. Evidence from human in-vivo studies is limited due to heterogeneity in study populations, small study samples, and technical limitations. Further research is necessary to reveal the role of the placenta in pathological circumstances. The placenta might thus be considered as the infants' black box of pregnancy. Results will contribute to more insights in the concept of fetal programming, which lays the foundations of optimum health, growth, and neurodevelopment across the lifespan.