Abstract

Alterations in maternal thyroid physiology may have deleterious consequences on the development of the fetal brain, but the underlying mechanisms remain elusive, hampering the development of appropriate therapeutic strategies. The present review sums up the contribution of genetically modified mouse models to this field. In particular, knocking out genes involved in thyroid hormone (TH) deiodination, transport, and storage has significantly improved the picture that we have of the economy of TH in the fetal brain and the underlying genetic program. These data pave the way for future studies to bridge the gap in knowledge between thyroid physiology and brain development.

Highlights

  • The major role of thyroid hormone (TH) in brain development has been recognized for a long time, but, in spite of considerable progress in the understanding of TH mode of action, the underlying mechanisms remain elusive

  • Thyroid hormone has for a long time been known to exert a major influence on human neurodevelopment, during prenatal and post-natal life

  • In the earliest neurodevelopmental stages, TH is present at very low levels in the celomic and amniotic fluids, while TH levels are high in the maternal serum

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Summary

Sabine Richard and Frédéric Flamant*

Institut de Génomique Fonctionnelle de Lyon, INRA USC 1370, Université de Lyon, Université Lyon 1, CNRS UMR 5242, Ecole Normale Supérieure de Lyon, Lyon, France. Alterations in maternal thyroid physiology may have deleterious consequences on the development of the fetal brain, but the underlying mechanisms remain elusive, hampering the development of appropriate therapeutic strategies. The present review sums up the contribution of genetically modified mouse models to this field. In parti­ cular, knocking out genes involved in thyroid hormone (TH) deiodination, transport, and storage has significantly improved the picture that we have of the economy of TH in the fetal brain and the underlying genetic program. These data pave the way for future studies to bridge the gap in knowledge between thyroid physiology and brain development

INTRODUCTION
TIME COURSE OF TH ACTION DURING HUMAN BRAIN NEURODEVELOPMENT
CONSEQUENCES OF TH DEFICIENCY ON HUMAN NEURODEVELOPMENT
THE MOUSE AS A MODEL OF HUMAN PREGNANCY
NEURODEVELOPMENTAL CONSEQUENCES OF CONGENITAL HYPOTHYROIDISM IN RODENTS
TH TRANSPORTERS
Findings
FUTURE DIRECTIONS AND CLINICAL RELEVANCE
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