A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration
A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration
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DOI：
10.1210/en.2004-0274
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发表时间：
2004-09-01
期刊：
影响因子：
4.8
通讯作者：
Berbel, P
中科院分区：
文献类型：
--
作者：
Ausó, E;Lavado-Autric, R;Berbel, P
流行病学研究和病例报告表明，即使是相对较小程度的母亲低甲状腺素血症在妊娠前半期是潜在的危险，最佳胎儿神经发育。我们的实验方法的目的是导致在皮质生成开始时，在一个温和的和短暂的母亲低甲状腺素血症。正常大鼠母鼠从胚胎第12天（E12）至E15只接受致甲状腺肿剂2-巯基-1-甲基咪唑3天。母体甲状腺激素一过性下降至正常血清值的70%，无甲状腺功能减退症的临床体征。从E14-E16或E17-E19，在3天期间每天向母鼠注射5-溴-2 '-脱氧尿苷（BrdU）。出生后39天（P39）测试其幼仔的听源性癫痫发作敏感性，并在P40时处死。通过免疫细胞化学鉴定掺入BrdU的细胞，并进行定量：发现许多异位细胞，无论是在E14-E16还是E17-E19标记，都被鉴定为神经元。在83%的幼鼠的躯体感觉皮层和海马中，BrdU标记的神经元的细胞结构和径向分布受到显著影响。γ-氨基丁酸能神经元的径向分布是正常的。在E13和E15之间输注T-4母鼠避免了这些变化，当T-4输注延迟至E15-E18时，这些变化无法预防。总的来说，52%的新生儿出生的甲状腺肿治疗的母鼠回应了一个声音刺激与野生运行，其次是癫痫发作。当外推到男性时，这些结果强调在孕中期前预防低甲状腺素血症的必要性，无论是中度还是潜在原因。
Epidemiological studies and case reports show that even a relatively minor degree of maternal hypothyroxinemia during the first half of gestation is potentially dangerous for optimal fetal neurodevelopment. Our experimental approach was designed to result in a mild and transient period of maternal hypothyroxinemia at the beginning of corticogenesis. Normal rat dams received the goitrogen 2-mercapto-1-methylimidazole for only 3 d, from embryonic d 12 (E12) to E15. Maternal thyroid hormones decreased transiently to 70% of normal serum values, without clinical signs of hypothyroidism. Dams were injected daily with 5-bromo-2'-deoxyuridine (BrdU) during 3 d, from E14-E16 or E17-E19. Their pups were tested for audiogenic seizure susceptibility 39 d after birth (P39) and killed at P40. Cells that had incorporated BrdU were identified by immunocytochemistry, and quantified: numerous heterotopic cells were found, whether labeled at E14-E16 or E17-E19, that were identified as neurons. The cytoarchitecture and the radial distribution of BrdU-Iabeled neurons was significantly affected in the somatosensory cortex and hippocampus of 83% of the pups. The radial distribution of gamma-aminobutyric acidergic neurons was, however, normal. The infusion of dams with T-4 between E13 and E15 avoided these alterations, which were not prevented when the T-4 infusion was delayed to E15-E18. In total, 52% of the pups born to the goitrogen-treated dams responded to an acoustic stimulus with wild runs, followed in some by seizures. When, extrapolated to man, these results stress the need for prevention of hypothyroxinemia before midpregnancy, however moderate, and whichever the underlying cause.