Sheep fetal iodine deficiency

Potter BJ, Mano MT, Balling GB, Rogers PS, Martin DM and Hetzel BS (1981) Reversal of brain retardation in iodine-deficient fetal sheep. In Howell I, McC, Gawthome JM, White CL, eds. Trace Element Metabolism in Man and Animals, pp. 313-315. Springer Verlag Berlin, Heidelberg, New York. 

Iodine Deficiency Disorders (IDD) are a major international public health problem (1). The effects of iodine deficiency occur at all ages, but are particularly important during the period of fetal development. The available epidemiological evidence has been complemented by experimental studies of fetal development in animal models. These have focussed particularly on fetal brain development because of its obvious importance Definite effects have been observed in a variety of animal models - the rat, the marmoset and the sheep. In addition studies of the mechanisms involved have been carried out which have revealed the importance of maternal thyroid function for fetal brain development. 

The sheep has been used as an animal model for extensive studies on iodine deficiency because of its convenience for the study of maternal-fetal function (6). 

Table 3. Effect of severe iodine deficiency on fetal brain development in the sheep. ... 

Table A. Histological data at lAO days gestation of brain regions from fetal sheep during severe dietary iodine deficiency (mean values). ...

The effects of severe iodine deficiency on fetal brain and somatic development were found to be more severe but similar to those observed by McIntosh et al (10) when thyroidectomy was performed on fetal sheep at 50-60 days. Fetal thyroidectomy later in gestation at 98 days caused less severe effects (11). Further investigations by McIntosh et al (12), following earlier indications (13) that the maternal thyroid could exert an influence on fetal development in early pregnancy, revealed that a combination of maternal thyroidectomy before conception and fetal thyroidectomy at 98 days gestation produced more severe effects than those of iodine deficiency (Fig. 1). 

In the light of the available data and observations on the sheep, it may be concluded that the effects of severe iodine deficiency are mediated by a combination of maternal and fetal hypothyroidism, the effect of maternal hypothyroidism being earlier than the onset of fetal thyroid secretion. This would infer an effect on neuroblast multiplication which... 

This is further indicated by evidence of the relation of maternal thyroxine levels to the risk of cretinism and the psychomotor defect from studies in Papua New Guinea (26). The subsequent lack of fetal thyroid hormones due to the inadequate supply of iodine in iodine deficiency would exacerbate the effects of maternal thyroid insufficiency and the combination of effects, which were represented experimentally in the sheep by maternal thyroidectomy before conception (21) combined with fetal thyroidectomy at 98 days (12), might be expected to produce the multiple defects of neurological cretinism. 

Animal models in the marmoset and the sheep have been developed to study the effect of severe iodine deficiency on brain development. Both these models are characterised by the production of severe maternal and fetal hypothyroidism which is associated with effects on the maturation of the cerebral cortex and cerebellum. There was a reduced brain weight with a reduced number of cells as indicated by reduced DNA, a greater density of cells in the cerebral cortex and reduced cell acquisition in the cerebellum. 

Studies of the mechanisms involved have been carried out in the sheep. The findings reveal significant, though less severe, effects of fetal thyroidectomy (late gestation) and a significant effect of maternal thyroidectomy on brain development in mid gestation. A combination of maternal and fetal thyroidectomy has similar but more severe effects than iodine deficiency. 

Cragg, B.G., Marshall, J., Wellby, M.L. and Hetzel, B.S. Retarded fetal brain development resulting from severe dietary iodine deficiency in sheep. Neuropath, appl. Neurobiology 8 303-313 (1982). 

Chavadej, J. and Hetzel, B.S. Restoration of Brain Growth in Fetal Sheep after Iodized Oil Administration to Pregnant Iodine-deficient Ewes. J. Neurological Sci. 66 15-26 (1984). 

To further establish the relation between iodine deficiency and fetal brain development, an animal model was developed in the pregnant sheep given an iodine-deficient diet. Subsequently, similar models were developed in the primate marmoset monkey and in the rat. 

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