Does PBDE (DE-71) induced developmental hypothyroxinemia correlate with behavioral effects in the rat?

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Abstract

Thyroid hormones are crucial during pre- and postnatal life for proper development of the brain. Developmental hypothyroxinemia results in hyperactivity and learning impairments in both rats and humans. For the anti-thyroid drug propylthiouracil (PTU) decreased maternal serum thyroxine (T4) levels in rat correlate with hyperactivity and learning impairments in the offspring. In the present study we pursued to establish the same correlation between decreased T4 and neurobehavioral changes for a class of environmental thyroid disrupting compounds; the polybrominated diphenyl ethers (PBDEs).
In an a large developmental toxicity study (n=20-21) time-mated Wistar rat dams were dosed with a technical penta-PBDE mixture (DE-71) from gestation day 7 through postnatal day (PND) 16 in doses of 0, 40, and 60 mg/kg/day. Serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured at various points in time in dams and offspring. The activity of the hypothalamic-pituitary axis was assessed by measuring thyroid gland weights and quantitative thyroid histology. In one male and one female per litter, motor activity levels were determined on PND 21 and PND 79, and cognition was assessed in the Morris water maze, at 19 weeks of age.
T4 and T3 levels were decreased dose-dependently in the dams on gestation day 15. The pups from all three dose groups were also markedly hypothyroxinemic during the entire postnatal period, with T4 reductions of ~70% at 2 weeks of age. However, the hypothalamic-pituitary-thyroid axis was not activated as TSH levels, thyroid weights and histopathology were unaffected. Activity and learning were likewise unaffected.
In conclusion, DE-71 induced profound hypothyroxinemia during development without causing behavioral changes in the rat offspring, despite a robust study design. The observed hypothyroxinemia was comparable to one induced by PTU and which caused behavioral effects correlating with serum T4 levels. Further studies are needed to elucidate the reasons for the dissimilar behavioral effects of DE-71 and PTU although similar effects on T4 are found.
Original languageEnglish
Publication date2015
Number of pages1
Publication statusPublished - 2015
Event8th Copenhagen Workshop on Endocrine Disruptors - COW 2015 - Copenhagen, Denmark
Duration: 27 Apr 201530 Apr 2015

Conference

Conference8th Copenhagen Workshop on Endocrine Disruptors - COW 2015
CountryDenmark
CityCopenhagen
Period27/04/201530/04/2015

Cite this

Ramhøj, L., Petersen, M. A., Egebjerg, K. M., Christiansen, S., & Hass, U. (2015). Does PBDE (DE-71) induced developmental hypothyroxinemia correlate with behavioral effects in the rat?. Abstract from 8th Copenhagen Workshop on Endocrine Disruptors - COW 2015, Copenhagen, Denmark.
Ramhøj, Louise ; Petersen, Marta Axelstad ; Egebjerg, Karen Mandrup ; Christiansen, Sofie ; Hass, Ulla. / Does PBDE (DE-71) induced developmental hypothyroxinemia correlate with behavioral effects in the rat?. Abstract from 8th Copenhagen Workshop on Endocrine Disruptors - COW 2015, Copenhagen, Denmark.1 p.
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abstract = "Thyroid hormones are crucial during pre- and postnatal life for proper development of the brain. Developmental hypothyroxinemia results in hyperactivity and learning impairments in both rats and humans. For the anti-thyroid drug propylthiouracil (PTU) decreased maternal serum thyroxine (T4) levels in rat correlate with hyperactivity and learning impairments in the offspring. In the present study we pursued to establish the same correlation between decreased T4 and neurobehavioral changes for a class of environmental thyroid disrupting compounds; the polybrominated diphenyl ethers (PBDEs).In an a large developmental toxicity study (n=20-21) time-mated Wistar rat dams were dosed with a technical penta-PBDE mixture (DE-71) from gestation day 7 through postnatal day (PND) 16 in doses of 0, 40, and 60 mg/kg/day. Serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured at various points in time in dams and offspring. The activity of the hypothalamic-pituitary axis was assessed by measuring thyroid gland weights and quantitative thyroid histology. In one male and one female per litter, motor activity levels were determined on PND 21 and PND 79, and cognition was assessed in the Morris water maze, at 19 weeks of age.T4 and T3 levels were decreased dose-dependently in the dams on gestation day 15. The pups from all three dose groups were also markedly hypothyroxinemic during the entire postnatal period, with T4 reductions of ~70{\%} at 2 weeks of age. However, the hypothalamic-pituitary-thyroid axis was not activated as TSH levels, thyroid weights and histopathology were unaffected. Activity and learning were likewise unaffected.In conclusion, DE-71 induced profound hypothyroxinemia during development without causing behavioral changes in the rat offspring, despite a robust study design. The observed hypothyroxinemia was comparable to one induced by PTU and which caused behavioral effects correlating with serum T4 levels. Further studies are needed to elucidate the reasons for the dissimilar behavioral effects of DE-71 and PTU although similar effects on T4 are found.",
author = "Louise Ramh{\o}j and Petersen, {Marta Axelstad} and Egebjerg, {Karen Mandrup} and Sofie Christiansen and Ulla Hass",
year = "2015",
language = "English",
note = "8th Copenhagen Workshop on Endocrine Disruptors - COW 2015 ; Conference date: 27-04-2015 Through 30-04-2015",

}

Ramhøj, L, Petersen, MA, Egebjerg, KM, Christiansen, S & Hass, U 2015, 'Does PBDE (DE-71) induced developmental hypothyroxinemia correlate with behavioral effects in the rat?', 8th Copenhagen Workshop on Endocrine Disruptors - COW 2015, Copenhagen, Denmark, 27/04/2015 - 30/04/2015.

Does PBDE (DE-71) induced developmental hypothyroxinemia correlate with behavioral effects in the rat? / Ramhøj, Louise; Petersen, Marta Axelstad; Egebjerg, Karen Mandrup; Christiansen, Sofie; Hass, Ulla.

2015. Abstract from 8th Copenhagen Workshop on Endocrine Disruptors - COW 2015, Copenhagen, Denmark.

Research output: Contribution to conferenceConference abstract for conferenceResearchpeer-review

TY - ABST

T1 - Does PBDE (DE-71) induced developmental hypothyroxinemia correlate with behavioral effects in the rat?

AU - Ramhøj, Louise

AU - Petersen, Marta Axelstad

AU - Egebjerg, Karen Mandrup

AU - Christiansen, Sofie

AU - Hass, Ulla

PY - 2015

Y1 - 2015

N2 - Thyroid hormones are crucial during pre- and postnatal life for proper development of the brain. Developmental hypothyroxinemia results in hyperactivity and learning impairments in both rats and humans. For the anti-thyroid drug propylthiouracil (PTU) decreased maternal serum thyroxine (T4) levels in rat correlate with hyperactivity and learning impairments in the offspring. In the present study we pursued to establish the same correlation between decreased T4 and neurobehavioral changes for a class of environmental thyroid disrupting compounds; the polybrominated diphenyl ethers (PBDEs).In an a large developmental toxicity study (n=20-21) time-mated Wistar rat dams were dosed with a technical penta-PBDE mixture (DE-71) from gestation day 7 through postnatal day (PND) 16 in doses of 0, 40, and 60 mg/kg/day. Serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured at various points in time in dams and offspring. The activity of the hypothalamic-pituitary axis was assessed by measuring thyroid gland weights and quantitative thyroid histology. In one male and one female per litter, motor activity levels were determined on PND 21 and PND 79, and cognition was assessed in the Morris water maze, at 19 weeks of age.T4 and T3 levels were decreased dose-dependently in the dams on gestation day 15. The pups from all three dose groups were also markedly hypothyroxinemic during the entire postnatal period, with T4 reductions of ~70% at 2 weeks of age. However, the hypothalamic-pituitary-thyroid axis was not activated as TSH levels, thyroid weights and histopathology were unaffected. Activity and learning were likewise unaffected.In conclusion, DE-71 induced profound hypothyroxinemia during development without causing behavioral changes in the rat offspring, despite a robust study design. The observed hypothyroxinemia was comparable to one induced by PTU and which caused behavioral effects correlating with serum T4 levels. Further studies are needed to elucidate the reasons for the dissimilar behavioral effects of DE-71 and PTU although similar effects on T4 are found.

AB - Thyroid hormones are crucial during pre- and postnatal life for proper development of the brain. Developmental hypothyroxinemia results in hyperactivity and learning impairments in both rats and humans. For the anti-thyroid drug propylthiouracil (PTU) decreased maternal serum thyroxine (T4) levels in rat correlate with hyperactivity and learning impairments in the offspring. In the present study we pursued to establish the same correlation between decreased T4 and neurobehavioral changes for a class of environmental thyroid disrupting compounds; the polybrominated diphenyl ethers (PBDEs).In an a large developmental toxicity study (n=20-21) time-mated Wistar rat dams were dosed with a technical penta-PBDE mixture (DE-71) from gestation day 7 through postnatal day (PND) 16 in doses of 0, 40, and 60 mg/kg/day. Serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured at various points in time in dams and offspring. The activity of the hypothalamic-pituitary axis was assessed by measuring thyroid gland weights and quantitative thyroid histology. In one male and one female per litter, motor activity levels were determined on PND 21 and PND 79, and cognition was assessed in the Morris water maze, at 19 weeks of age.T4 and T3 levels were decreased dose-dependently in the dams on gestation day 15. The pups from all three dose groups were also markedly hypothyroxinemic during the entire postnatal period, with T4 reductions of ~70% at 2 weeks of age. However, the hypothalamic-pituitary-thyroid axis was not activated as TSH levels, thyroid weights and histopathology were unaffected. Activity and learning were likewise unaffected.In conclusion, DE-71 induced profound hypothyroxinemia during development without causing behavioral changes in the rat offspring, despite a robust study design. The observed hypothyroxinemia was comparable to one induced by PTU and which caused behavioral effects correlating with serum T4 levels. Further studies are needed to elucidate the reasons for the dissimilar behavioral effects of DE-71 and PTU although similar effects on T4 are found.

M3 - Conference abstract for conference

ER -

Ramhøj L, Petersen MA, Egebjerg KM, Christiansen S, Hass U. Does PBDE (DE-71) induced developmental hypothyroxinemia correlate with behavioral effects in the rat?. 2015. Abstract from 8th Copenhagen Workshop on Endocrine Disruptors - COW 2015, Copenhagen, Denmark.