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Fluoride-induced thyroid proliferative changes and their reversal in female mice and their pups.Abstract
To determine effects of fluoride on thyroid function in suckling mice, adult female mice were given 500 ppm NaF (226 ppm F–) in their drinking water from the 15th day of pregnancy until either the 4th or 14th day after parturition. On day 14 of full-period treatment, pups and their mothers were sacrificed. In the F– exposed group the body weight of the 14-day-old pups was 15% less than the controls. This reduction in pup body weight is attributed to a defect in plasma thyroid hormone levels: free thyroxine (FT4: –15%) and free triiodothyronine (FT3: –6%). These reductions also correlate with a decrease in thyroid iodine content of the experimental pups (–55%) and their mothers (–68%), along with hypertrophy of their thyroid glands (+29% in the pups and +41% in the mothers), probably caused by a 1.74- and 3.15-fold increase of plasma thyroid stimulating hormone (TSH) in the pups and their mothers, respectively. These biochemical modifications also correspond histologically with an increase in thyroid follicular number and a reduction in colloid volume. When fluoride ion was eliminated from the mothers’ drinking water four days following parturition, a partial recovery occurred after ten days in body weight, thyroid gland weight, and plasma TSH level in both pups and their mothers. However, essentially complete recovery was observed in plasma levels of FT4 and FT3 and in thyroid iodine content. Compared with NaF-treated mice, significant amelioration in thyroid histological aspects was also observed after withdrawal of NaF treatment.