The influence of maternal hypothyroxinaemia on early brain and placental development was examined in a partially thyroidectomized (parathyroid-spared; TX) rat dam model. Ornithine decarboxylase (ODC) specific activity, along with more general indices of cell growth, were determined in prenatal whole brain (at 15, 19 and 22 days of gestation), postnatal brain regions (at 5, 10 and 14 days) and placenta.
Maternal hypothyroxinaemia resulted in reductions in fetal body weight, brain weight, brain DNA content and brain total protein content at 15 days of gestation; the latter effect persisting until 19 days of gestation. Further changes in brain cell growth were observed near term, when an increase in the DNA concentration was accompanied by a decrease in the total protein: DNA ratio. Growth of the postnatal brain regions appeared normal, with the exception of an isolated increase in the protein content of the cerebellum at postnatal day 5. Determination of the specific activity of brain ODC revealed a complex pattern of change in the progeny of TX dams, super-imposed upon the normal ontogenetic decline. In the fetal brain, activity was initially deficient at 15 days of gestation but was increased at 22 days of gestation relative to controls. The compromise extended into the postnatal period; ODC specific activity being transiently reduced in the brainstem, the subcortex and the cerebral cortex. Placental development was less consistently affected; wet weight, gross indices of cell growth (DNA content, DNA concentration, total protein: DNA ratio) and ODC specific activity were all normal in the TX dam. However, cytosolic and total protein concentrations were reduced at 15 and 19 days of gestation respectively.
These results demonstrate abnormal fetal brain cell development as a consequence of maternal hypothyroxinaemia. The damage extended into the neonatal period, well after the onset of fetal thyroid hormone synthesis. Although the reduced supply of maternal thyroxine to the fetal brain may play a major role in this dysgenesis, factors such as the impairment of placental function must be taken into consideration.