Maternal thyroid hormones early in pregnancy and fetal brain development

During the last few decades our understanding of the possible role of thyroid hormones during brain development has increased and contributed to resolve previously discordant hypotheses, although much remains to be clarified. Thyroid hormones of maternal origin are present in the fetal compartment, despite the very efficient uterine-placental 'barrier', necessary to avoid potentially toxic concentrations of free T4 and T3 from reaching fetal tissues before they are required for development. T3 remains low throughout pregnancy, whereas FT4 in fetal fluids increases rapidly to adult levels, and is determined by the maternal availability of T4. It is present in embryonic fluids 4 weeks after conception, with FT4 steadily increasing to biologically relevant values. T3, generated from T4 in the cerebral cortex, reaches adult values by mid-gestation and is partly bound to specific nuclear receptor isoforms. lodothyronine deioidinases are important for the spatial and temporal regulation of T3 bioavailability, tailored to the differing and changing requirements of thyroid hormone-sensitive genes in different brain structures, but other regulatory mechanism(s) are likely to be involved. Maternal transfer constitutes a major fraction of fetal serum T4, even after onset of fetal thyroid secretion, and continues to have an important protective role in fetal neurodevelopment until birth. Prompt treatment of maternal hypothyroidism, identified by increased TSH, is being advocated to mitigate a negative effect on the woman and her child. However, even a moderate transient period of maternal hypothyroxinemia at the beginning of rat neurogenesis disrupts neuronal migration into cortical layers. These findings reinforce the epidemiological evidence that early maternal hypothyroxinemia-when neuronal migratory waves are starting-is potentially damaging for the child. Detection of an inappropiate first trimester FT4 surge that may not result in increased TSH, may be crucial for the prevention of learning disabilities in a significant number of unborn children.