Early developmental exposure to sodium perchlorate disrupts thyroid, liver, and testicular development in mice

Perchlorate is an endocrine-disrupting compound (EDC) used for its oxidative properties and has been detected in many industrialized countries in drinking water, soil, foods, and breast milk. Perchlorate competitively inhibits the uptake of iodide into the thyroid, thus reducing thyroid hormone synthesis. Perchlorate causes steatosis in the liver, alters gonadal development, and increases tubule size in kidneys in some fish models but not others. Much less is known of perchlorate's effects on mammals with respect to these organs. We examined the morphological effects of environmentally relevant concentrations (0 ppm, 10 ppm, and 100 ppm) of sodium perchlorate on the thyroid, liver, kidneys, testes, and ovaries on mice exposed from conception. Sexually mature female mice were randomly divided into the three treatment groups, bred, and exposed to perchlorate via water until offspring were weaned at postnatal day 36 (P36). Offspring continued exposure for 49 days at the same concentration as their mother, euthanized at P85, whole body perfused with 4% paraformaldehyde, and target organs were dissected, sectioned, and stained using hematoxylin and eosin. Perchlorate-exposed mice displayed a significant decrease in colloid area and a significant increase in follicle density, angiogenesis, and lipid accumulation within the thyroid. The liver showed a significant increase in the presence of ballooned hepatocytes and lipid accumulation. Within the kidney, we found perchlorate significantly altered nephron tubule thickness. In the testes, perchlorate exposure caused an increase in disorganized seminiferous tubules, an increase in Leydig cell nuclei area. and an increase in the size of blood vessels. There were no effects observed in the ovaries of perchlorate-exposed mice compared to the control. These results indicate many commonalities among fishes and other mammalian models but also the need for understanding disparate results between model species.