Maternal thyroid status regulates the expression of neuronal and astrocytic cytoskeletal proteins in the fetal brain

Maternal thyroid hormone (TH) crosses the placenta and is postulated to reg ulate fetal brain development. However, TH-dependent stages of fetal brain development remain to be characterised. We have therefore compared the leve ls 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 secre tion, which occurs at 17.5 days gestation (dg) in the rat. Maternal hypothyroidism disrupted fetal growth, so that fetal body and brai n weights were reduced near term. Vimentin expression was unaffected, howev er, indicating normal acquisition of neuronal and glial precursor cells. Fe tal 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 a lpha -internexin, the earliest neurofilament protein expressed in fetal bra in were reduced at 16 dg in TX dams, but increased at 21 dg. The ontogeny o f neurofilament-L was also perturbed in these pregnancies, with deficient l evels 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 br ain development. Early disturbances in neuronal differentiation are not cor rected by the onset of fetal TH secretion. Such disturbances may contribute to the neurological damage observed in children born to hypothyroxinaemic mothers.