Iodine insufficiency exacerbates structural defect in rat brain following developmental exposure to ammonium perchlorate
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Iodine is required for thyroid hormone (TH) synthesis, severe deficiencies in this micronutrient leading to hypothyroidism. As thyroid hormone is necessary for brain development, maintaining iodine status is especially important during pregnancy. Perchlorate is an environmental contaminant that interferes with iodine uptake and reduces TH synthesis. In this study we examined how dietary iodine deficiency and perchlorate exposure, alone and in combination affect serum TH profiles in pregnant rats and their offspring. Pups were examined on postnatal day (PN) 14 for the presence of a periventricular heterotopia (PVH), a known TH-dependent phenotype within the brain. Female rats were maintained on either an iodine-replete (Control) vs iodine deficient (ID) diet for a minimum of 4 weeks, reducing serum T4 ~35% prior to breeding. On gestational day 6, half of each dietary group was exposed to 0 or 300 ppm perchlorate via the drinking water. Serum T4 in newborn pups was decreased ~20% by ID or perchlorate, but had rebounded by PN6. In contrast, serum T4 in offspring of dams exposed to both ID and perchlorate was decreased by 57% in the neonate, with further decrements apparent on PN14. Pups from perchlorate- exposed dams exhibited very small PVH. Although mean volumes were statistically indistinguishable from background in controls, small heterotopia were evident in 6/10 of animals examined, while pups from ID dams did not differ from controls. In contrast, this phenotype was present in all pups born to ID and perchlorate-exposed dams (12/12), and quantified volume indicates a severe effect (mean volume of 0.0542 mm3). These findings indicate that the effects of perchlorate exposure are greatly exacerbated under conditions of dietary iodine insufficiency and produce permanent structural defects within the developing brain.