Prevalence of Periventricular Heterotopia within Adult Rats Following Developmental Exposure to Perchlorate and Dietary Iodine Deficiency
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Thyroid hormones (THs) are crucial for neurodevelopment; insufficiency during human pregnancy causes irreversible deficits. Iodine homeostasis is critical to thyroid health, and severe dietary iodine deficiency (ID) results in hypothyroidism. Some environmental toxicants can also interfere with iodine status and impair TH production. A brain defect, a periventricular heterotopia (PVH) has been described in hypothyroid rat pups. PVH result from mismigration of neurons and are present in a variety of neurodevelopmental disorders. To date, PVH have not been reported in response to ID or exposure to environmental contaminants. In this study we examined brains of offspring of pregnant rats exposed to marginal dietary iodine insufficiency and/or moderate doses of the environmental contaminant perchlorate for the presence of PVH. Female LE rats were maintained on either iodine replete (225ng/g) or deficient (25ng/g) diets for a minimum of 4wks. Sperm-positive females were then administered 0 or 300ppm perchlorate via drinking water beginning on gestational day 6 producing 4 treatment groups, 10-12 dams/group. On postnatal day 14, brains from pups (1 male,1 female/litter) were sectioned and prepared for NueN immunohistochemistry. Sections were examined for the presence of PVH, the area recorded, and volumes calculated. Mean PVH volumes did not differ between control, ID, and perchlorate-exposed pups. Pups born to ID dams receiving perchlorate exhibited PVH volumes exceeding >5000% over background levels in controls. These findings extend observations of PVH to environmental contaminants and demonstrate profound neurodevelopmental sequelae when perchlorate exposure occurs under conditions of iodine insufficiency. Does not reflect EPA policy.