Quantitative Adverse Outcome Pathway for Neurodevelopmental Effects of Thyroid Peroxidase-Induced Thyroid Hormone Synthesis Inhibition

Metadata Updated: February 23, 2019

Adequate levels of thyroid hormones (TH) are needed for proper brain development, deficiencies may lead to adverse neurological outcomes in humans and animal models. Environmental chemicals have been linked to TH disruption, yet the relationship between developmental exposures and decline in serum TH resulting in neurodevelopmental impairment is poorly understood. The present study developed a quantitative adverse outcome pathway (qAOP) where serum thyroxin (T4) reduction following inhibition of thyroperoxidase in the thyroid gland are described and related to deficits in fetal brain TH and the development of a brain malformation, subcortical band heterotopia. Pregnant dams were exposed to 6-propylthiouracil (PTU 0, 0.1, 0.5, 1, 2, or 3 ppm) from gestational day 6-20, increasing PTU concentrations in maternal thyroid gland and serum as well as in fetal serum. Dams exposed to 0.5 ppm PTU and higher exhibited dose-dependent decreases in thyroidal T4. Serum T4 levels in the dam were significantly decreased with exposure to 2 and 3 ppm PTU. In the fetus, T4 decrements were first observed at a lower dose of 0.5 ppm PTU. Based on these data, fetal brain T4 levels were estimated from published literature sources, and quantitatively linked to increases in the size of the heterotopia present in the brains of offspring. These data show the potential of in vivo assessments and computational descriptions of biological responses to predict the development of this structural brain malformation and use of qAOP approach to evaluate brain deficits that may result from exposure to other TH disruptors.

This dataset is associated with the following publication: Hassan, I., H. El-Masri, P. Kosian, J. Ford, S. Degitz, and M. Gilbert. Neurodevelopment and Thyroid Hormone Synthesis Inhibition in the Rat: Quantitative Understanding Within the Adverse Outcome Pathway Framework. TOXICOLOGICAL SCIENCES. Society of Toxicology, 57-73, (2017).

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Public: This dataset is intended for public access and use. License: See this page for license information.

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References

https://dx.doi.org/10.1093/toxsci/kfx163

Dates

Metadata Created Date November 30, 2017
Metadata Updated Date February 23, 2019

Metadata Source

Harvested from EPA ScienceHub

Additional Metadata

Resource Type Dataset
Metadata Created Date November 30, 2017
Metadata Updated Date February 23, 2019
Publisher U.S. EPA Office of Research and Development (ORD)
Unique Identifier https://doi.org/10.23719/1390120
Maintainer
Mary Gilbert
Maintainer Email
Public Access Level public
Bureau Code 020:00
Schema Version https://project-open-data.cio.gov/v1.1/schema
Datagov Dedupe Retained 20190222230752
Harvest Object Id bddf62dd-084c-4bee-8f69-8e7caeefceb9
Harvest Source Id cf9b0004-f9fd-420e-bade-a86839e82acf
Harvest Source Title EPA ScienceHub
License https://pasteur.epa.gov/license/sciencehub-license.html
Data Last Modified 2017-03-23
Program Code 020:000
Publisher Hierarchy U.S. Government > U.S. Environmental Protection Agency > U.S. EPA Office of Research and Development (ORD)
Related Documents https://dx.doi.org/10.1093/toxsci/kfx163
Source Datajson Identifier True
Source Hash 9128eb156dbfaa184e69ec5306c1438a5a42031d
Source Schema Version 1.1

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