Sampson D, Pickard M R, Sinha A K, Evans I M, Leonard A J, Ekins R P
Division of Molecular Endocrinology, University College London Medical School, Mortimer Street, London W1N 8AA, UK.
J Endocrinol. 2000 Dec;167(3):439-45. doi: 10.1677/joe.0.1670439.
Maternal thyroid hormone (TH) crosses the placenta and is postulated to regulate fetal brain development. However, TH-dependent stages of fetal brain development remain to be characterised. We have therefore compared the levels of several neuronal and glial cytoskeletal proteins in fetal brains from normal (N) and partially thyroidectomised (TX) rat dams by immunoblotting. Pregnancies were studied both before and after the onset of fetal TH secretion, which occurs at 17.5 days gestation (dg) in the rat. Maternal hypothyroidism disrupted fetal growth, so that fetal body and brain weights were reduced near term. Vimentin expression was unaffected, however, indicating normal acquisition of neuronal and glial precursor cells. Fetal brain levels of glial fibrillary acidic protein (GFAP) were reduced at 21 dg, suggesting delayed astrocytic differentiation, although regression analysis demonstrated appropriate GFAP levels for brain weight. Levels of alpha-internexin, the earliest neurofilament protein expressed in fetal brain were reduced at 16 dg in TX dams, but increased at 21 dg. The ontogeny of neurofilament-L was also perturbed in these pregnancies, with deficient levels apparent at both 16 and 21 dg. These effects on neuronal cytoskeletal proteins were unrelated to fetal brain growth retardation. These findings confirm that maternal hypothyroidism disrupts early fetal brain development. Early disturbances in neuronal differentiation are not corrected by the onset of fetal TH secretion. Such disturbances may contribute to the neurological damage observed in children born to hypothyroxinaemic mothers.
母体甲状腺激素（TH）可穿过胎盘，并被推测对胎儿大脑发育起调节作用。然而，胎儿大脑发育中依赖TH的阶段仍有待明确。因此，我们通过免疫印迹法比较了正常（N）和部分甲状腺切除（TX）大鼠母鼠所产胎鼠大脑中几种神经元和神经胶质细胞骨架蛋白的水平。研究了妊娠大鼠在胎儿TH分泌开始之前和之后的情况，大鼠的胎儿TH分泌始于妊娠第17.5天（dg）。母体甲状腺功能减退会干扰胎儿生长，导致足月时胎儿体重和脑重降低。然而，波形蛋白的表达未受影响，这表明神经元和神经胶质前体细胞的正常获得。在21 dg时，胎儿大脑中胶质纤维酸性蛋白（GFAP）的水平降低，提示星形胶质细胞分化延迟，尽管回归分析显示GFAP水平与脑重相符。在TX母鼠所产胎鼠中，最早在胎儿大脑中表达的神经丝蛋白α-中间丝蛋白在16 dg时水平降低，但在21 dg时升高。在这些妊娠中，神经丝-L的个体发育也受到干扰，在16 dg和21 dg时水平均明显不足。这些对神经元细胞骨架蛋白的影响与胎儿脑生长迟缓无关。这些发现证实母体甲状腺功能减退会干扰胎儿早期大脑发育。胎儿TH分泌开始后，神经元分化的早期干扰并未得到纠正。这种干扰可能导致甲状腺素水平低的母亲所生孩子出现神经损伤。
