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

Abstract

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 -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.

The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia

“…59,60 Maternal glucocorticoid 61,62 and thyroid 63 hormones can cross the blood placental barrier and are essential for normal fetal neurodevelopment. 64,65 However, in humans, exposure of the fetus to excess glucocorticoids can have detrimental effects on fetal brain development 64,66 and hypothyroidism during pregnancy is associated with impaired cognitive and motor function in children. 67,68 Alternatively, the behavioral deficits observed in the adult offspring of rodents exposed to LPS during pregnancy could be the consequence of neurodevelopmental changes in the fetal brain resulting from LPS-dependent changes in the body temperature of the pregnant dam (i.e.…”

The Effects of Maternal Hyperthyroidism on Histologic Changes in Parietal Lobe in Rat Embryos

“…The experimental groups on average showed a reduction in the thickness of layers and a reduction in the number of cells compared with the control group. The results of histomorphometry and cell counting in a study showed that the mother's affliction with hyperthyroid disease during pregnancy controlled cell multiplication in the external granular layer of the cerebellum and diminished the neural migration in the inner layer towards the side of the cortical area [23,24]. It seems that maternal hyperthyroidism also causes a delay to occur in embryonic brain growth, because the shortage of thyroid hormone in the embryotic period causes unnatural growth and a lack of distinction in cerebellum cells.…”

Influence of maternal hyperthyroidism in the rat on the expression of neuronal and astrocytic cytoskeletal proteins in fetal brain

“…Recently, we have shown that maternal hypothyroidism can also disturb the ontogeny of these proteins in fetal brain, as well as that of -internexin (INX) -the earliest appearing neuronal specific intermediate filament (Sampson et al 2000). In the present study, we have investigated the hypothesis that chronic moderate maternal hyperthyroidism also impairs neuronal and astrocytic differentiation.…”

“…Early neuronal maturation, in particular, appears compromised (Evans et al 1999, Sampson et al 2000, with some deficits persisting in postnatal life (Porterfield & Hendrich 1991, Pickard et al 1997, Evans et al 1999.…”