THE INFLUENCE OF THE MATERNAL THYROID-HORMONE ENVIRONMENT DURING PREGNANCY ON THE ONTOGENY OF BRAIN AND PLACENTAL ORNITHINE DECARBOXYLASE ACTIVITY IN THE RAT

The influence of maternal hypothyroxinaemia on early brain and placent al development was examined in a partially thyroidectomized (parathyro id-spared; TX) rat dam model. Ornithine decarboxylase (ODC) specific a ctivity, along with more general indices of cell growth, were determin ed in prenatal whole brain (at 15, 19 and 22 days of gestation), postn atal brain regions (at 5, 10 and 14 days) and placenta. Maternal hypot hyroxinaemia resulted in reductions in fetal body weight, brain weight , brain DNA content and brain total protein content at 15 days of gest ation; the latter effect persisting until 19 days of gestation. Furthe r changes in brain cell growth were observed near term, when an increa se in the DNA concentration was accompanied by a decrease in the total protein: DNA ratio. Growth of the postnatal brain regions appeared no rmal, with the exception of an isolated increase in the protein conten t of the cerebellum at postnatal day 5. Determination of the specific activity of brain ODC revealed a complex pattern of change in the prog eny of TX dams, superimposed upon the normal ontogenetic decline. In t he fetal brain, activity was initially deficient at 15 days of gestati on 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 cere bral 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 i n the TX dam. However, cytosolic and total protein concentrations were reduced at 15 and 19 days of gestation respectively. These results de monstrate abnormal fetal brain cell development as a consequence of ma ternal hypothyroxinaemia. The damage extended into the neonatal period , well after the onset of fetal thyroid hormone synthesis. Although th e reduced supply of maternal thyroxine to the fetal brain may play a m ajor role in this dysgenesis, factors such as the impairment of placen tal function must be taken into consideration.