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Iodized oil was administered as a single intramuscular injection to pregnant iodine-deficient ewes at 100 days gestation and the subsequent growth of their fetuses compared with that of fetuses of severely iodine-deficient ewes and of iodine-replete ewes, all of which were fed the same low-iodine diet. The administered iodine produced a remarkable improvement in thyroid function and physical appearance of the fetuses, accompanied by an increase in brain growth and to a lesser extent in body growth, which at 140 days was only slightly (but significantly) less than that of the controls. There was restoration of the number of cells (DNA) and myelination (cholesterol/DNA) in the cerebellum and cerebral hemispheres which suggests a catch-up of neuroblast development during pregnancy. Histological examination, however, revealed that counts of synapses (density) in the cerebral cortex after iodized oil were still less than those of the control fetal brains. The relevance of these findings to the effects of iodine deficiency on human brain development is discussed.

The common cotton-eared marmoset (Callithrix jacchus jacchus) has been used for the first time as a primate model to study the effects of dietary iodine deficiency on fetal brain development. Paired male and female marmosets were fed a low-iodine diet of maize, peas, meat meal, Torula yeast, maize oil and added vitamins, minerals and amino acids for 6 months before mating. Offspring from first and second pregnancies were compared with offspring from control marmosets fed the same diet but supplemented with iodine. Severe iodine deficiency in the fetus at birth was evident by reduced plasma thyroxine levels, increased plasma thyroid stimulating hormone levels, increased thyroid weight and reduced thyroid iodine content. Thyroid histology revealed hyperplasia, hypertrophy and absence of colloid material in the follicles. Iodine deficiency caused a reduction in the weight of the fetal brain and in particular the cerebellum. Brain cell number was reduced in the cerebellum and brainstem but cell size was reduced in the cerebral hemispheres. Histology of the brain revealed morphological changes in the cerebellum and cerebral hemispheres. In the-cerebellum there was: an increase in the thickness of the external germinal layer indicative of impaired cell acquisition; a decrease in total area; a decrease in molecular layer area; and an increase in Purkinje cell (Pc) linear density due to a reduction in the length of the Pc line. The decrease in molecular layer area and increase in Pc linear density imply diminished ascending and lateral extension of Pc dendrites. Changes in the cerebral hemispheres consisted of an increase in the density of neuronal cell bodies in the granular band and a decrease in synaptic counts in the layer between the pia mater and supragranular band of the visual cortex. Offspring from second pregnancies compared to those from first pregnancies were more severely affected and associated with lower plasma levels of maternal and fetal thyroxine. These findings indicate the importance of maternal and fetal thyroid function in relation to fetal brain development in the primate.