Sheep have been used to study the effect of dietary iodine deficiency on the development of the fetal brain. Severe iodine deficiency caused reduction in fetal brain and body weights and in brain DNA and protein from 70 days gestation to parturition. The lowered brain weight and brain DNA at 70 days gestation indicates a reduced number of cells, probably due to slower neuroblast multiplication which normally occurs from 40-80 days in the sheep, and the reduction in DNA and protein after 80 days implies that the development of neuroglia could be slowed also in iodine deficiency. Morphological changes were observed in both the cerebral hemispheres and the cerebellum. In the cerebral hemispheres of the iodine-deficient fetuses an increased density of neurons was apparent histologically in the motor cortex and visual cortex and in the CA1 and CA4 areas of the hippocampus in comparison with controls. In the cerebellum there was delayed migration of cells from the external granular layer to the internal granular layer and increased density of Purkinje cells in the iodine-deficient fetal brains. In addition, the molecular area was increased and the medullary area reduced in comparison with controls. These change are indicative of delayed brain maturation. Evidence of fetal hypothyroidism was provided by low fetal thyroid iodine and plasma T4 values, thyroid hyperplasia from 70 days gestation, significant reduction in body weight at the same time as the brain retardation, and absence of wool growth and delayed skeletal maturation near parturition. It is apparent from the biochemical and histological changes observed during iodine deficiency that iodine is an essential element for normal fetal brain and physical development in the sheep.

Animals↗

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A change in susceptibility of rat cerebellar Purkinje cells to damage by alcohol during fetal, neonatal and adult life.

The sensitivity of rat cerebellar Purkinje cells to ethanol exposure during fetal, neonatal or adult life was assessed by histological techniques. Pregnant female rats were exposed to ethanol vapour during the last 2 weeks of gestation. Purkinje cells were counted 5 days after the pups were born. The number of Purkinje cells in lobe VIII was reduced by 45%, and the linear density of Purkinje cells in lobe I was 47% less than in controls not exposed to ethanol. Smaller reductions were found in other lobes. The weight of the cerebellum was reduced by 34%. Neonatal rats were exposed to ethanol vapour briefly during daylight hours on the third and fourth days after birth. Purkinje cells were counted on the fifth day after birth, and losses similar to those described above were found, with additional significant reductions of cell numbers in lobe I and of Purkinje cell density in lobe VIII. The weight of the cerebellum was reduced by only 4%. Adult male rats were exposed to ethanol vapour for 3 weeks and no Purkinje cell losses were subsequently found. The dura overlying the cerebellum of separate adult male rats was superfused with 100% ethanol for 1 h and no abnormalities were detected with electron microscopy in the exposed cortex 6 days later. It is remarkable that the brief neonatal treatment caused a more widespread loss of Purkinje cells than the 10 days of exposure to ethanol in utero, whereas the Purkinje cells present in adult animals show a great resistance to ethanol. The neonatal period seems to be a time of high susceptibility of Purkinje cells to ethanol.

Animals↗

PubMedDate not supplied

A change in susceptibility of rat cerebellar Purkinje cells to damage by acetaldehyde during fetal, neonatal and adult life.

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Acetaldehyde↗

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The effect of maternal and fetal thyroidectomy on fetal brain development in the sheep.

The combination of maternal and fetal thyroidectomy was found to have a significant influence on brain development in the fetal sheep at 140 days. There was reduced body weight (36%), brain weight (23%), DNA (26%) and protein (34%) content in five fetuses of ewes, subjected to thyroidectomy six weeks before mating and fetal thyroidectomy at 98 days gestation, compared with six sham operated controls. Cholesterol content was also reduced (36%) and water content increased (2.4%). The cerebellum was most severely affected and showed histologically an increased cell density associated with a significant reduction in the ratio of the molecular to granular cell layer area. The cell density was also significantly increased in the CA1 region of the hippocampus, but not in the CA4 region. It was also increased in the parietal layer of the cerebral cortex but not in the motor region. There was a significant reduction in the weight of heart (28.6%) and lungs (33.4%), while the kidneys and pituitary were enlarged (20.5% and 48.5% respectively) as a result of double thyroidectomy. The combined thyroidectomy was similar to iodine deficiency in its effect on fetal brain development, indicating that it is probable that iodine deficiency has its effects in the sheep by a combination of maternal and fetal hypothyroidism.

Animals↗