Citation:

Ramhoj, L., U. Hass, C. Wood, M. Gilbert, D. Usai, J. Boberg, A. Vinggaard, AND M. Axelstad. Developmental Exposure to Perfluorohexane Sulfonate (PFHxS) induces hypothyroxinemia in Rat Dams and Offspring: Examination of the Thyroid Gland and Behavior. American Thyroid Association, Washington, DC, October 03 - 07, 2018.

Impact/Purpose:

It is well accepted that thyroid hormone (TH) disruption during pregnancy can induce severe intellectual disability in the developing child. However, it is not understood how less severe disturbances to the thyroid axis may affect neurodevelopment. This issue is of high importance given that many environmental contaminants, like pesticides perfluorinated compounds, alter serum TH concentrations in laboratory animals. This study examine a perflourinated chemical, PFHxS to determine potential mode of action and to determine if indices of brain function were altered following developmental exposure in a rodent model. Neither thyroid genes, liver genes, or brain genes were altered in offpsring despite significant reductions in serum TH in dams and offspring. These data suggest that either serum markers do not always indicate changes in brain function or metrics used to examine neurodevelopmental outcomes in this study were not sufficiently sensitive.

Description:

Introduction Thyroid hormones (TH) are critical for mammalian brain development. In humans, low maternal serum thyroxine (T4) levels are associated with neurological deficiencies and cognitive impairment. Perfluorohexane sulfonate (PFHxS) is a widespread environmental contaminant found in human serum, tissues and milk. We have shown that PFHxS decrease serum thyroxine in pregnant rat dams and their offspring. Here, we further investigate effects on the thyroid system, neurodevelopment, and combination effects of PFHxS and a mixture of environmentally relevant endocrine disruptors. Methods Perfluorohexane sulfonate (PFHxS, 0, 0.05, 5 or 25 mg/kg/day with and without EDmix, a mixture of 12 endocrine disruptors e.g. phthalates, pesticides, UV-filters, Bisphenol A and butyl paraben) was administered (p.o.) to Wistar rat dams (n = 16-20/dose group) from gestation day (GD) 7 through postnatal day (PD) 22. Offspring were assessed in activity boxes and the radial arm maze. Results/discussion PFHxS not only decreased serum T4 levels in dams and offspring but in the high dose also reduced T3 to 84% of controls in both dams (PD 22) and pups (PD 16). The hypothalamic-pituitary-thyroid (HPT) axis was not activated based on lack of effect on serum TSH, thyroid gland histology, weight and thyroid gene expression levels. Developmental hypothyroxinemia did not appear to increase physical activity levels in young and adult offspring. However, the expected sex difference was absent on PD 115 in low dose PFHxS (0.05 mg/kg) and at high doses in combination with EDmix (5 mg/kg +EDmix and 25 mg/kg + EDmix). Slight effects on offspring learning and memory did not appear correlated to decreased TH levels during development. Conclusions PFHxS decreased circulating levels of T3 and T4 in pregnant rat dams and their offspring without apparent compensation by the HPT axis. The thyroid hormone disruption was not associated with detectable learning and memory deficits. Rather findings suggest that PFHxS may disrupt sexual differentiation of the brain. Standard behavioral assays appear insensitive to adverse effects on brain development caused by thyroid hormone disruption. Hence, there is a need for development of sensitive assays to protect human thyroid function. Does not reflect EPA policy.

Record Details: