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 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.
Sampson
D
D
Division of Molecular Endocrinology, University College London Medical School, Mortimer Street, London W1N 8AA, UK.
Pickard
M R
MR
Sinha
A K
AK
Evans
I M
IM
Leonard
A J
AJ
Ekins
R P
RP
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000737:chemistry; D001921:Brain / Q000196:embryology*; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000032:analysis; D003598:Cytoskeletal Proteins / Q000032:analysis*; D005314:Embryonic and Fetal Development; D005260:Female; D005865:Gestational Age; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D015151:Immunoblotting; D007381:Intermediate Filament Proteins; D016014:Linear Models; D016900:Neurofilament Proteins / Q000032:analysis; D009474:Neurons / Q000737:chemistry; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000196:embryology / Q000502:physiology*; D013965:Thyroidectomy; D014746:Vimentin / Q000032:analysis
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D016900:Neurofilament Proteins; D014746:Vimentin; C046643:alpha-internexin; C044882:neurofilament protein L