Severe Hypothyroxinemia, But No Behavioural or Auditory Effects in Rats, After Developmental Exposure to a Brominated Flame Retardant

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Abstract

In all mammalian species, correct levels of thyroid hormones are important for proper brain development. In humans, a number of studies have shown that even mild maternal hypothyroxinemia during pregnancy is associated with impaired fetal brain development. Therefore exposure to chemicals that reduce human thyroid hormone levels could have detrimental consequences, both for the affected individuals and for society as a whole. In rats, developmental hypothyroidism induced by exposure to potent anti-thyroid drugs like propyl thiouracil (PTU), has been shown to causes adverse effects on brain development. Here we investigated whether exposure to a brominated flame retardant, known to act as a thyroid disrupter in rats, would also cause neurobehavioral changes. Time-mated Wistar rat dams (n=20) were dosed with a polybrominated diphenyl ether (PBDE) called DE-71. Exposure was from gestation day (GD) 7 through postnatal day (PND) 16 at doses of 0, 40, and 60 mg/kg/day. Serum thyroxine (T4), triiodothyronine (T3) and thyroid-stimulating hormone (TSH) were measured at various time points in dams and offspring, along with thyroid gland weights and histopathology. In the offspring, motor activity was determined on PND 21 and PND 79, cognition was assessed in a Morris water maze at 19 weeks of age, and hearing was assessed at 6 months of age by test of otoacoustic emission. In the dams, T4 and T3 levels were significantly decreased on GD 15 in both dose groups. Furthermore, the pups from both dose groups showed T4 reductions of ~70% on PND 16. However, postnatal body weights, TSH levels, thyroid gland weights and histopathology were unaffected by DE-71 treatment, as were motor activity levels, learning and hearing ability.This lack of effects in a validated battery of behavioral tests testing was surprising, because similar T4 reductions had previously caused significant effects on activity, learning and hearing ability in our PTU study. Further studies, investigating structural abnormalities in the brains of developmentally hypothyroid animals, could be used to elucidate why compounds showing T4 decreases of similar magnitudes cause such different effect on behavior. However, the present results indicate that the mode of action of a thyroid disrupting chemical is important with regards to its adverse effects on rodent brain development.
Original languageEnglish
Publication date2016
Number of pages1
Publication statusPublished - 2016
Event55th Annual Meeting and ToxExpo - New Orleans, United States
Duration: 13 Mar 201617 Mar 2016

Conference

Conference55th Annual Meeting and ToxExpo
CountryUnited States
CityNew Orleans
Period13/03/201617/03/2016

Cite this

@conference{b4bcd75ed14647ef8f52fa05856a5f28,
title = "Severe Hypothyroxinemia, But No Behavioural or Auditory Effects in Rats, After Developmental Exposure to a Brominated Flame Retardant",
abstract = "In all mammalian species, correct levels of thyroid hormones are important for proper brain development. In humans, a number of studies have shown that even mild maternal hypothyroxinemia during pregnancy is associated with impaired fetal brain development. Therefore exposure to chemicals that reduce human thyroid hormone levels could have detrimental consequences, both for the affected individuals and for society as a whole. In rats, developmental hypothyroidism induced by exposure to potent anti-thyroid drugs like propyl thiouracil (PTU), has been shown to causes adverse effects on brain development. Here we investigated whether exposure to a brominated flame retardant, known to act as a thyroid disrupter in rats, would also cause neurobehavioral changes. Time-mated Wistar rat dams (n=20) were dosed with a polybrominated diphenyl ether (PBDE) called DE-71. Exposure was from gestation day (GD) 7 through postnatal day (PND) 16 at doses of 0, 40, and 60 mg/kg/day. Serum thyroxine (T4), triiodothyronine (T3) and thyroid-stimulating hormone (TSH) were measured at various time points in dams and offspring, along with thyroid gland weights and histopathology. In the offspring, motor activity was determined on PND 21 and PND 79, cognition was assessed in a Morris water maze at 19 weeks of age, and hearing was assessed at 6 months of age by test of otoacoustic emission. In the dams, T4 and T3 levels were significantly decreased on GD 15 in both dose groups. Furthermore, the pups from both dose groups showed T4 reductions of ~70{\%} on PND 16. However, postnatal body weights, TSH levels, thyroid gland weights and histopathology were unaffected by DE-71 treatment, as were motor activity levels, learning and hearing ability.This lack of effects in a validated battery of behavioral tests testing was surprising, because similar T4 reductions had previously caused significant effects on activity, learning and hearing ability in our PTU study. Further studies, investigating structural abnormalities in the brains of developmentally hypothyroid animals, could be used to elucidate why compounds showing T4 decreases of similar magnitudes cause such different effect on behavior. However, the present results indicate that the mode of action of a thyroid disrupting chemical is important with regards to its adverse effects on rodent brain development.",
author = "Petersen, {Marta Axelstad} and Louise Ramh{\o}j and Egebjerg, {Karen Mandrup} and Ulla Hass",
year = "2016",
language = "English",
note = "55th Annual Meeting and ToxExpo ; Conference date: 13-03-2016 Through 17-03-2016",

}

Severe Hypothyroxinemia, But No Behavioural or Auditory Effects in Rats, After Developmental Exposure to a Brominated Flame Retardant. / Petersen, Marta Axelstad; Ramhøj, Louise; Egebjerg, Karen Mandrup; Hass, Ulla.

2016. Abstract from 55th Annual Meeting and ToxExpo, New Orleans, United States.

Research output: Contribution to conferenceConference abstract for conferenceResearchpeer-review

TY - ABST

T1 - Severe Hypothyroxinemia, But No Behavioural or Auditory Effects in Rats, After Developmental Exposure to a Brominated Flame Retardant

AU - Petersen, Marta Axelstad

AU - Ramhøj, Louise

AU - Egebjerg, Karen Mandrup

AU - Hass, Ulla

PY - 2016

Y1 - 2016

N2 - In all mammalian species, correct levels of thyroid hormones are important for proper brain development. In humans, a number of studies have shown that even mild maternal hypothyroxinemia during pregnancy is associated with impaired fetal brain development. Therefore exposure to chemicals that reduce human thyroid hormone levels could have detrimental consequences, both for the affected individuals and for society as a whole. In rats, developmental hypothyroidism induced by exposure to potent anti-thyroid drugs like propyl thiouracil (PTU), has been shown to causes adverse effects on brain development. Here we investigated whether exposure to a brominated flame retardant, known to act as a thyroid disrupter in rats, would also cause neurobehavioral changes. Time-mated Wistar rat dams (n=20) were dosed with a polybrominated diphenyl ether (PBDE) called DE-71. Exposure was from gestation day (GD) 7 through postnatal day (PND) 16 at doses of 0, 40, and 60 mg/kg/day. Serum thyroxine (T4), triiodothyronine (T3) and thyroid-stimulating hormone (TSH) were measured at various time points in dams and offspring, along with thyroid gland weights and histopathology. In the offspring, motor activity was determined on PND 21 and PND 79, cognition was assessed in a Morris water maze at 19 weeks of age, and hearing was assessed at 6 months of age by test of otoacoustic emission. In the dams, T4 and T3 levels were significantly decreased on GD 15 in both dose groups. Furthermore, the pups from both dose groups showed T4 reductions of ~70% on PND 16. However, postnatal body weights, TSH levels, thyroid gland weights and histopathology were unaffected by DE-71 treatment, as were motor activity levels, learning and hearing ability.This lack of effects in a validated battery of behavioral tests testing was surprising, because similar T4 reductions had previously caused significant effects on activity, learning and hearing ability in our PTU study. Further studies, investigating structural abnormalities in the brains of developmentally hypothyroid animals, could be used to elucidate why compounds showing T4 decreases of similar magnitudes cause such different effect on behavior. However, the present results indicate that the mode of action of a thyroid disrupting chemical is important with regards to its adverse effects on rodent brain development.

AB - In all mammalian species, correct levels of thyroid hormones are important for proper brain development. In humans, a number of studies have shown that even mild maternal hypothyroxinemia during pregnancy is associated with impaired fetal brain development. Therefore exposure to chemicals that reduce human thyroid hormone levels could have detrimental consequences, both for the affected individuals and for society as a whole. In rats, developmental hypothyroidism induced by exposure to potent anti-thyroid drugs like propyl thiouracil (PTU), has been shown to causes adverse effects on brain development. Here we investigated whether exposure to a brominated flame retardant, known to act as a thyroid disrupter in rats, would also cause neurobehavioral changes. Time-mated Wistar rat dams (n=20) were dosed with a polybrominated diphenyl ether (PBDE) called DE-71. Exposure was from gestation day (GD) 7 through postnatal day (PND) 16 at doses of 0, 40, and 60 mg/kg/day. Serum thyroxine (T4), triiodothyronine (T3) and thyroid-stimulating hormone (TSH) were measured at various time points in dams and offspring, along with thyroid gland weights and histopathology. In the offspring, motor activity was determined on PND 21 and PND 79, cognition was assessed in a Morris water maze at 19 weeks of age, and hearing was assessed at 6 months of age by test of otoacoustic emission. In the dams, T4 and T3 levels were significantly decreased on GD 15 in both dose groups. Furthermore, the pups from both dose groups showed T4 reductions of ~70% on PND 16. However, postnatal body weights, TSH levels, thyroid gland weights and histopathology were unaffected by DE-71 treatment, as were motor activity levels, learning and hearing ability.This lack of effects in a validated battery of behavioral tests testing was surprising, because similar T4 reductions had previously caused significant effects on activity, learning and hearing ability in our PTU study. Further studies, investigating structural abnormalities in the brains of developmentally hypothyroid animals, could be used to elucidate why compounds showing T4 decreases of similar magnitudes cause such different effect on behavior. However, the present results indicate that the mode of action of a thyroid disrupting chemical is important with regards to its adverse effects on rodent brain development.

M3 - Conference abstract for conference

ER -