D. Sampson et al., Maternal thyroid status regulates the expression of neuronal and astrocytic cytoskeletal proteins in the fetal brain, J ENDOCR, 167(3), 2000, pp. 439-445
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.