Evaluating thyroid hormone disruption: investigations of long-term neurodevelopmental effects in rats after perinatal exposure to perfluorohexane sulfonate (PFHxS)
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Evaluating thyroid hormone disruption : investigations of long-term neurodevelopmental effects in rats after perinatal exposure to perfluorohexane sulfonate (PFHxS). / Ramhøj, Louise; Hass, Ulla; Gilbert, Mary E.; Wood, Carmen; Svingen, Terje; Usai, Diana; Vinggaard, Anne Marie; Mandrup, Karen; Axelstad, Marta.
I: Scientific Reports, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Evaluating thyroid hormone disruption
T2 - investigations of long-term neurodevelopmental effects in rats after perinatal exposure to perfluorohexane sulfonate (PFHxS)
AU - Ramhøj, Louise
AU - Hass, Ulla
AU - Gilbert, Mary E.
AU - Wood, Carmen
AU - Svingen, Terje
AU - Usai, Diana
AU - Vinggaard, Anne Marie
AU - Mandrup, Karen
AU - Axelstad, Marta
PY - 2020
Y1 - 2020
N2 - Thyroid hormones are critical for mammalian brain development. Thus, chemicals that can affect thyroid hormone signaling during pregnancy are of great concern. Perfluorohexane sulfonate (PFHxS) is a widespread environmental contaminant found in human serum, breastmilk, and other tissues, capable of lowering serum thyroxine (T4) in rats. Here, we investigated its effects on the thyroid system and neurodevelopment following maternal exposure from early gestation through lactation (0.05, 5 or 25 mg/kg/day PFHxS), alone or in combination with a mixture of 12 environmentally relevant endocrine disrupting compounds (EDmix). PFHxS lowered thyroid hormone levels in both dams and offspring in a dose-dependent manner, but did not change TSH levels, weight, histology, or expression of marker genes of the thyroid gland. No evidence of thyroid hormone-mediated neurobehavioral disruption in offspring was observed. Since human brain development appear very sensitive to low T4 levels, we maintain that PFHxS is of potential concern to human health. It is our view that current rodent models are not sufficiently sensitive to detect adverse neurodevelopmental effects of maternal and perinatal hypothyroxinemia and that we need to develop more sensitive brain-based markers or measurable metrics of thyroid hormone-dependent perturbations in brain development.
AB - Thyroid hormones are critical for mammalian brain development. Thus, chemicals that can affect thyroid hormone signaling during pregnancy are of great concern. Perfluorohexane sulfonate (PFHxS) is a widespread environmental contaminant found in human serum, breastmilk, and other tissues, capable of lowering serum thyroxine (T4) in rats. Here, we investigated its effects on the thyroid system and neurodevelopment following maternal exposure from early gestation through lactation (0.05, 5 or 25 mg/kg/day PFHxS), alone or in combination with a mixture of 12 environmentally relevant endocrine disrupting compounds (EDmix). PFHxS lowered thyroid hormone levels in both dams and offspring in a dose-dependent manner, but did not change TSH levels, weight, histology, or expression of marker genes of the thyroid gland. No evidence of thyroid hormone-mediated neurobehavioral disruption in offspring was observed. Since human brain development appear very sensitive to low T4 levels, we maintain that PFHxS is of potential concern to human health. It is our view that current rodent models are not sufficiently sensitive to detect adverse neurodevelopmental effects of maternal and perinatal hypothyroxinemia and that we need to develop more sensitive brain-based markers or measurable metrics of thyroid hormone-dependent perturbations in brain development.
U2 - 10.1038/s41598-020-59354-z
DO - 10.1038/s41598-020-59354-z
M3 - Journal article
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 2672
ER -
ID: 361830605