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).

Raw data to accompanying manuscript "The Pollutant Perfluorohexane Sulfonate (PFHxS) Reduces Serum Thyroxine but Does Not Alter Thyroid Hormone Action in the Postnatal Rat Brain". This dataset is associated with the following publication: O'Shaughnessy, K., K. Bell, A. Sasser, M. Gilbert, C. Riutta, J. Ford, J. McCord, and C. Wood. The Pollutant Perfluorohexane Sulfonate (PFHxS) Reduces Serum Thyroxine but Does Not Alter Thyroid Hormone Action in the Postnatal Rat Brain. ENVIRONMENT INTERNATIONAL. Elsevier B.V., Amsterdam, NETHERLANDS, 190: 108838, (2024).

This file contains summary data of thyroid hormones in serum and brain in rat dams and their pups following maternal exposure to a perflorinated substance, PFHxS and an antimicrobial, Triclosan. Gene expression in thyroid glands and liver and brain were investigated. Anatomical and bahavioral indices of developmental neurotoxicity were assessed. Result so fall of these inquiries are summarized in these datasets. This dataset is associated with the following publication: Gilbert, M.E., K. OShaughnessy, S. Thomas, C. Riutta, C. Wood, A. Smith, W. Oshiro, J. Ford, A. Hotchkiss, I. Hassan, and R.L. Ford. Thyroid Disruptors: Extrathyroidal Sites of Chemical Action and Neurodevelopmental Outcome-An Examination Using Triclosan and Perfluorohexane Sulfonate. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 183(6): 195-213, (2021).

This file contains summary data of thyroid hormones in serum and brain in rat dams and their pups following maternal exposure to a perflorinated substance, PFHxS and an antimicrobial, Triclosan. Gene expression in thyroid glands and liver and brain were investigated. Anatomical and bahavioral indices of developmental neurotoxicity were assessed. Result so fall of these inquiries are summarized in these datasets. This dataset is associated with the following publication: Gilbert, M.E., K. OShaughnessy, S. Thomas, C. Riutta, C. Wood, A. Smith, W. Oshiro, J. Ford, A. Hotchkiss, I. Hassan, and R.L. Ford. Thyroid Disruptors: Extrathyroidal Sites of Chemical Action and Neurodevelopmental Outcome-An Examination Using Triclosan and Perfluorohexane Sulfonate. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 183(6): 195-213, (2021).

Thyroid hormones (THs) control normal brain development and function in humans, and identifying environmental thyroid disrupting chemicals has significant public health implications. As such, some developmental and reproductive toxicology studies now require or suggest serum total thyroxine (T4) measurements in pregnant, lactating, and developing rats. However, serum T4 concentrations are normally low in the fetus and pup which makes accurate quantification difficult. These challenges can be circumvented by technologies like mass spectrometry, but these approaches are expensive and not always widely available. To demonstrate the feasibility of measuring serum T4 using a commercially available kit we compare T4 concentrations in pregnant, fetal, and neonatal rats, as measured by both liquid chromatography mass spectrometry (LC/MS/MS) and radioimmunoassay (RIA). The sera samples analyzed were obtained from rats on gestational day 20 (dams and fetuses) or postnatal day 5 (pups), following a maternal exposure to the goitrogen propylthiouracil (0-3 ppm) to incrementally decrease T4. We show that with optimization, it is possible to measure serum T4 using low sample volumes (25-50μL) by RIA and the relative control values obtained are comparable to LC/MS/MS. This work demonstrates that low concentrationT4 quantification is feasible for toxicological studies, but attention to technical detail is pertinent. This dataset is associated with the following publication: O'Shaughnessy, K., M. Hotchkiss, A. Buckalew, A. Murr, M. Gilbert, and T. Stoker. An optimized radioimmunoassay for quantification of total serum thyroxine (T4) in fetal, neonatal, and pregnant rats. NEUROTOXICOLOGY AND TERATOLOGY. Elsevier Science Ltd, New York, NY, USA, 100: 107303, (2023).

Structural defects in the rat brain associated with maternal exposure to ammonium perchlorate accompanied reductions in circulating levels of thyroid hormone in the dam and the fetus. The magnitude of the effect was small relative to other thyroid hormone disruptors, but his was due to the lack of sufficient bioavailability of perchlorate to the nursing neonate. When pups were administered perchlorate directly for the first 6 days of life or if perchlorate was administered under conditions of maternal dietary iodine deficiency, very large brain malformations were induced. This dataset is associated with the following publication: Gilbert, M., K. O'Shaughnessy, K. Bell, and J. Ford. Structural Malformations in the Neonatal Rat Brain Accompany Developmental Exposure to Ammonium Perchlorate. Toxics. MDPI, Basel, SWITZERLAND, 11(12): 1027, (2023).

This dataset contains results from rodent study. Thyroid hormones and brain endpoints are reported for pregnant rat dams and progeny on gestational day 20 following drinking water exposure to the dams. Several dose levels were examined. This dataset is associated with the following publication: Gilbert, M., I. Hassan, C. Wood, K. O'Shaughnessy, S. Spring, S. Thomas, and J. Ford. Gestational Exposure to Perchlorate in the rat: Thyroid Hormones in Fetal Thyroid Gland, Serum, and Brain. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 188(1): 117-130, (2022).

behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil. Electrophysiological measures of 'memory' in form of plasticity model known as long term potentiation (LTP) Molecular changes induced by LTP. This dataset is associated with the following publication: Gilbert , M., K. Sanchez-Huerta, and C. Wood. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Make Rats. ENDOCRINOLOGY. Endocrine Society, 157(2): 774-87, (2016).

behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil. Electrophysiological measures of 'memory' in form of plasticity model known as long term potentiation (LTP) Molecular changes induced by LTP. This dataset is associated with the following publication: Gilbert , M., K. Sanchez-Huerta, and C. Wood. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Make Rats. ENDOCRINOLOGY. Endocrine Society, 157(2): 774-87, (2016).

Raw data accompanying "Thyroid Hormone Action Controls Multiple Components of Cell Junctions at the Ventricular Zone in the Newborn Rat Brain". This dataset is associated with the following publication: O'Shaughnessy, K., B. McMichael, A. Sasser, K. Bell, C. Riutta, J. Ford, T. Stoker, R. Grindstaff, A. Pandiri, and M. Gilbert. Thyroid Hormone Action Controls Multiple Components of Cell Junctions at the Ventricular Zone in the Newborn Rat Brain. Frontiers in Endocrinology. Frontiers, Lausanne, SWITZERLAND, 14: 1090081, (2023).