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).

Perchlorate is an environmental contaminant that interferes with iodine uptake via the NIS transporter into the thyroid gland, reducing thyroid hormone (TH) synthesis. As adequate supplies of TH are essential for brain development, exposures to perchlorate during pregnancy have raised concern for the developing brain. This paper describes the effects of exposure of pregnant rat dams to a classic chemical NIS inhibitor, perchlorate, on serum, thyroid gland and brain in the dam and pup. declines were observed in the newborn pup. TH were also reduced in the newborn pup brain, but both serum and brain hormones quickly recovered by PN2 despite continued maternal exposure. Gene expression changes in the gland revealed dramatic increases in expression of Nis, serum perchlorate concentrations fell, and large increases in serum TSH were evident. Combined, these events contributed to rapid recovery of serum markers in the early postnatal period. Despite full recovery of serum and brain hormones, significant reductions in a number of molecular markers of TH-action remained in the cortex and hippocampus of the PN14 pup brain. The findings provide for the first-time quantitative information collected in the same study for thyroid hormones in the thyroid gland, serum, and brain. They provide essential quantitative data to reduce uncertainties in development of Physiologically Based Pharmacokinetic (PBPK), Biologically Based Dose Response (BBDR), and Quantitative Adverse Outcome (qAOP) models of thyroid disruption and neurodevelopment. They demonstrate the remarkable resilience of the neonatal thyroid gland to NIS inhibition and support the use of Comparative Thyroid Assay (CTA) for identifying thyroid system disrupting chemicals. They indicate that the postnatal rat may be much less sensitive to the neurological effects of TH insufficiency relative to humans based on species differences in the timing of brain development. This dataset is associated with the following publication: Gilbert, M., I. Hassan, K. O'Shaughnessy, C. Wood, T. Stoker, C. Riutta, and J. Ford. Ammonium Perchlorate: Serum Dosimetry, Neurotoxicity and Resilience of the Neonatal Rat Thyroid System. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 198(1): 113-127, (2023).

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).

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).

This dataset includes information on rat dam and pup bodyweights, thyroid hormone concentrations in serum, gene expression in brain, cell counts for cell proliferation in brain. This dataset is associated with the following publication: OShaughnessy, K., S. Thomas, S. Spring, J. Ford, R. Ford, and M. Gilbert. A transient window of hypothyroidism alters neural progenitor cells and results in abnormal brain development. Scientific Reports. Nature Publishing Group, London, UK, 1-14, (2019).

This dataset includes information on rat dam and pup bodyweights, thyroid hormone concentrations in serum, gene expression in brain, cell counts for cell proliferation in brain. This dataset is associated with the following publication: OShaughnessy, K., S. Thomas, S. Spring, J. Ford, R. Ford, and M. Gilbert. A transient window of hypothyroidism alters neural progenitor cells and results in abnormal brain development. Scientific Reports. Nature Publishing Group, London, UK, 1-14, (2019).

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).

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).