Citation:

Thomas, R., K. Bell, C. Riutta, M. Hawks, J. Ford, AND M. Gilbert. Prevalence of Periventricular Heterotopia within Adult Rats Following Developmental Exposure to Perchlorate and Dietary Iodine Deficiency. Developmental Neurotoxicology Society (DNTS), Charleston, SC, June 24 - 28, 2023.

Impact/Purpose:

This work was conducted to provide quantitative information for the refinement of Adverse Outcome Pathways for thyroid disrupting chemicals and their potential impact on developing brain. In this report we demonstrate increased vulnerability of developing fetal brain to the exposure of a thyroid hormone disrupting chemical under conditions of dietary iodine deficiency. A structural malformation in the brains of offspring of rat dams is reported. This report updates previous work by expanding the observation to both male and female offspring with no sex-dependent differences in mean volumes detected. They provide further confidence in this outcome measure as a usable metric for brain-based thyroid disruption and demonstrate the need to consider dietary iodine status in evaluation of hazard characterization and risk.

Description:

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.

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