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The role of the placenta in thyroid hormone delivery to the fetus

Nature Clinical Practice Endocrinology & Metabolism volume 5, pages 45–54 (2009)Cite this article

Abstract

The transplacental passage of thyroid hormones from the maternal circulation to the fetal circulation within the human hemochorial placenta is important for normal fetal development, particularly the development of the central nervous system. The role of maternal thyroid hormones is particularly important in the first half of pregnancy, before the onset of endogenous thyroid hormone production in the fetus. The human placenta regulates the quantity and composition of different forms of transported thyroid hormones to ensure that the requisite levels are present in the fetus for each stage of development. Transplacental thyroid hormone supply to the fetus is modulated by several factors, including the following proteins: plasma membrane transporters, which regulate the passage of thyroid hormones in and out of cells; iodothyronine deiodinases, which metabolize thyroid hormones; and proteins within trophoblast cells, which bind thyroid hormones. In pathological situations of either maternal or fetal thyroid hormone deficiency during pregnancy, the placenta seems to lack the full compensatory mechanisms necessary to optimize maternal–fetal transfer of thyroid hormones. Inadequate passage of thyroid hormones can lead to suboptimal fetal thyroid hormone levels, which might contribute to the neurodevelopmental delay associated with such conditions. Thus, maintaining normal maternal thyroid hormone status is likely to be the primary factor in ensuring adequate transplacental thyroid hormone passage and appropriate iodide supply to the fetus.

Key Points

  • The transplacental passage of thyroid hormones from the maternal circulation to the fetal circulation is important from the first trimester of pregnancy to ensure normal fetal development, particularly of the central nervous system

  • In normal pregnancy, transplacental thyroid hormone passage is modulated by plasma membrane thyroid hormone transporters, the metabolism of thyroid hormones by iodothyronine deiodinases, and the binding of thyroid hormones to several different proteins within placental trophoblast cells

  • In pathological pregnancies with either maternal or fetal thyroid hormone deficiency, the placenta lacks the full compensatory mechanisms necessary to optimize maternal–fetal transfer of thyroid hormones to achieve normal thyroid hormone levels in the fetus

  • Maintaining normal maternal thyroid hormone status is likely to be the primary factor in determining adequate transplacental thyroid hormone passage and appropriate iodide supply to the fetus

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Figure 1: Changes in concentrations of maternal and fetal thyroid hormones in the fetal circulation during human gestation.
Figure 2: The human placenta and fetus during early and late pregnancy.
Figure 3: Cross-sections of a placental terminal chorionic villous in early and late pregnancy.
Figure 4: The passage of T4 and T3 through placental trophoblasts from the maternal to the fetal circulation during pregnancy.

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Acknowledgements

The authors acknowledge the significant contribution made to their work in the human placenta by their long-standing collaborators, Professor J Franklyn and Dr C McCabe. The authors' research is funded by the Health Foundation, the Medical Research Council (UK), Action Medical Research, and the University of Birmingham. Competing interests

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Authors and Affiliations

  1. SY Chan is a Clinician Scientist in Obstetrics, E Vasilopoulou is a PhD student, and MD Kilby is Professor of Fetal Medicine at the School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.,

    Shiao Y Chan, Elisavet Vasilopoulou & Mark D Kilby

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Correspondence to Mark D Kilby.

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Chan, S., Vasilopoulou, E. & Kilby, M. The role of the placenta in thyroid hormone delivery to the fetus. Nat Rev Endocrinol 5, 45–54 (2009). https://doi.org/10.1038/ncpendmet1026

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