Data for O'Shaughnessy et al. 2023 - Bypassing the Brain Barriers: Upregulation of Serum miR-495 and miR-543-3p Reflects Thyroid-Mediated Developmental Neurotoxicity in the Rat. This dataset is associated with the following publication: O'Shaughnessy, K., A. Sasser, K. Bell, C. Riutta, J. Ford, R. Grindstaff, and M. Gilbert. Bypassing the Brain Barriers: Upregulation of Serum miR-495 and miR-543-3p Reflects Thyroid-Mediated Developmental Neurotoxicity in the Rat. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 198(1): 128-140, (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).

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).

This study looked at functional endpoints in adult offspring of rats exposed in utero and postnatally to an environmentally relevant mixture of PCBs, Fox River blend. A model of neural plasticity and epilepsy, electrical kindling, was examined. Animals exposed to PCBs had slower kindling rates suggesting impaired plasticity mechanisms, consistent with previous work with PCBs where deficits were seen in another plasticity model, long-term potentiation. This dataset is associated with the following publication: Bandara, S., R. Sadowski, S. Schantz, and M. Gilbert. Developmental Exposure to an Environmental PCB Mixture Delays the Propagation of Kindling in the Amygdala. NEUROTOXICOLOGY. Elsevier B.V., Amsterdam, NETHERLANDS, n/a, (2016).

thyroid hormone from serum of rats exposed to goitrogen. Morphometry in brain. Behavioral data. This dataset is associated with the following publication: OShaughnessy, K., P. Kosian, J. Ford, W. Oshiro, S. Degitz, and M. Gilbert. Developmental Thyroid Hormone Insufficiency Induces Cortical Brain Malformation and Learning Impairments: A Cross-Fostering Study. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 163(1): 101-115, (2018).

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).

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).

File contains data on body, liver, thyroid weights from dams and exposed offspring, serum thyroid hormones, gland and cortical gene expression, results of cognitive function tests. This dataset is associated with the following publication: Ramhoj, L., U. Haas, M. Gilbert, C. Wood, T. Svingen, D. Usai, A.M. Vinggaard, K. Mandrup, and M. Axelstad. Evaluating thyroid hormone disruption: Investigations of long-term neurodevelopmental effects in rats after perinatal exposure to perfluorohexane sulfonate (PFHxS). Scientific Reports. Nature Publishing Group, London, UK, 10(1): 2672, (2020).

Biomarker Image Cytometry. The cell-level frequency of NK2 Homeobox 1 (NKX2-1), Keratin 7 (KRT7), and Thyroglobulin (TG) protein staining were quantitatively evaluated by high-content imaging across huThyrEC cell line variants (1-4) in two medium formulations (huThyrEC and h7H) for verification of thyroid follicular epithelial cell enrichment. Data are the % positive expression frequency (mean ± SD) of two replicates. This dataset is associated with the following publication: Hopperstad, K., T. Truschel, T. Wahlicht, W. Stewart, A. Eicher, T. May, and C. Deisenroth. Characterization of Novel Human Immortalized Thyroid Follicular Epithelial Cell Lines. Applied In Vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, USA, 7(2): 39-49, (2021).

180626 Thyroid Hormone PFOA PFOS Manuscript Data. This dataset is associated with the following publication: Selano, J., V. Richardson, J. Washington, and C. Mazur. Characterization of non-radiolabeled Thyroxine (T4) uptake in cryopreserved rat hepatocyte suspensions: Pharmacokinetic implications for PFOA and PFOS chemical exposure. TOXICOLOGY IN VITRO. Elsevier Science Ltd, New York, NY, USA, 58: 230-238, (2019).