Maternal thyroid hormones early in pregnancy and fetal brain development
Maternal thyroid hormones early in pregnancy and fetal brain development
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DOI：
10.1016/j.beem.2004.03.012
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发表时间：
2004-06-01
影响因子：
7.4
通讯作者：
del Rey, FE
中科院分区：
文献类型：
--
作者：
de Escobar, GM;Obregón, MJ;del Rey, FE
在过去的几十年里，我们对甲状腺激素在大脑发育过程中可能发挥的作用的理解有所增加，并有助于解决以前不一致的假设，尽管仍有许多问题有待澄清。母体来源的甲状腺激素存在于胎儿室中，尽管子宫-胎盘“屏障”非常有效，这是避免游离T4和T3在发育所需之前到达胎儿组织所必需的潜在毒性浓度。T3在整个怀孕期间保持较低水平，而胎儿体液中的FT 4迅速增加到成人水平，并由母亲的T4可用性决定。它存在于受孕后4周的胚胎液中，FT 4稳步增加到生物学相关值。T3由大脑皮层中的T4产生，在妊娠中期达到成人值，并部分与特定的核受体亚型结合。碘甲腺原氨酸脱碘酶对于T3生物利用度的空间和时间调节是重要的，针对不同脑结构中甲状腺激素敏感基因的不同和变化的需求而定制，但可能涉及其他调节机制。母体转移构成了胎儿血清T4的主要部分，即使在胎儿甲状腺分泌开始后，并且在胎儿神经发育中继续具有重要的保护作用，直到birth.Prompt治疗母体甲状腺功能减退症，通过增加TSH鉴定，被提倡减轻对妇女和她的孩子的负面影响。然而，即使是一个温和的短暂时期的母体低甲状腺素血症在大鼠神经发生的开始破坏神经元迁移到皮质层。这些发现加强了流行病学证据，即早期母体甲状腺素过少症--当神经元迁移波开始时--对孩子有潜在的损害。检测不适当的前三个月FT 4激增，可能不会导致TSH增加，可能是至关重要的，以防止学习障碍的显着数量的未出生的孩子。
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.