Retarded Fetal Brain Development Resulting From Severe Dietary Iodine Deficiency in Sheep

Abstract

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.

Early effects of iodine deficiency on radial glial cells of the hippocampus of the rat fetus. A model of neurological cretinism.

“…Permanent audiogenic seizure susceptibility was shown in adult progeny of severely iodinedeficient rats (45), but the timing of the initial damage was not defined. Iodine-deficient fetuses of ewes and newborn marmosets have been studied extensively, and the alterations in their brain morphology have been reported (46)(47)(48). Both these species are more mature at birth than humans: the fetal lambs and newborn marmosets were studied near term, at a period of CNS development which would be postnatal in humans.…”

Iodine deficiency and brain development in the first half of pregnancy

“…After being fed on the diet for five months the ewes were mated and foetuses were obtained 56, 70, 98 and 140 days later or nearing full term, and compared with age-matched controls from ewes given the same diet but supplemented either with KI or iodised oil injections 72 . The iodine deficient ewes had a markedly lower concentration of serum T 4 and a higher TSH concentration.…”

Development of Contrast Sensitivity in Infants with Prenatal and Neonatal Thyroid Hormone Insufficiencies

“…A lack of TH during fetal or early postnatal life is associated with specific brain damage. This includes abnormal neuronal proliferation and migration (2,3), decreased dendritic densities and synaptic profiles (4), impaired synaptic transmission (5), and reduced myelination (6). TH acts by regulating specific brain genes (7) through the formation of a nuclear receptor complex (8), which serves to up-or down-regulate specific genes (9) via a variety of signaling mechanisms (10,11).…”