Serum and brain thyroid hormone measurements in rat brain. This dataset is associated with the following publication: Gilbert, M., J. Ford, C. Riutta, K. OShaughnessy, and P.A. Kosian. Reducing Uncertainties in Quantitative Adverse Outcome Pathways by Analysis of Thyroid Hormone in the Neonatal Rat Brain. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 193(2): 192-203, (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).

Development of the neurovascular unit (NVU) is a complex, multistage process that requires orchestrated cell signaling mechanisms across several cell types and ultimately results in the formation of the blood-brain barrier. Typical high-throughput screening (HTS) assays investigate single biochemical or single cell responses following chemical insult. As the NVU comprises multiple cell types interacting at various stages of development, a methodology for combining high-throughput results across pertinent cell-based assays is needed to investigate potential chemical-induced disruption to the development of this complex cell system. To this end, we developed a novel method for screening putative NVU disruptors across diverse assay platforms to predict chemical perturbation of the developing NVU. Here, HTS assay results measuring chemical-induced perturbations to cellular key events across angiogenic and neurogenic outcomes were combined to create a cell-based prioritization of NVU hazard. Using activity from each biological outcome, chemicals were grouped into similar modes of action and used to train a logistic regression literature model. This model utilizes the chemical-specific pairwise mutual information score for PubMed MeSH annotations to represent how often a chemical was shown to produce a specific outcome in the published literature space. Taken together, this study presents a methodology to investigate NVU developmental hazard using cell-based HTS assays and literature evidence to prioritize screening of putative NVU disruptors. The results from these screening efforts demonstrate how chemicals that represent a range of putative vascular disrupting compound (pVDC) scores based on angiogenic endpoints can also produce effects on neurogenic outcomes such as neurite outgrowth, neuroprogenitor/neural crest migration, representing an additional method for understanding the range of possible modes of action for disruption of the developing NVU. This dataset is associated with the following publication: Zurlinden, T., K. Saili, N. Baker, T. Toimela, T. Heinonen, and T. Knudsen. A cross-platform approach to characterize and screen potential neurovascular unit toxicants. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 96(September 2020): 300-315, (2020).

We differentiated human induced pluripotent stem cells (hiPSCs) to embryonic endoderm and sought to identify a tipping point at which the developing system did not recover from perturbations caused by exposure to a known teratogen, all-trans retinoic acid (ATRA). Differentiating iPSC-derived endoderm was exposed to five concentrations of ATRA between 0.001 and 10 µM at 6h, 96h, or 192h and assessed for forkhead box A2 (FOXA2) protein expression and global gene transcript expression measured by RNA-sequencing. A tipping point of 17±11 nM was identified where patterns of differentially expressed genes supported a shift in the developmental trajectory away from embryonic endoderm in favor of mesoderm and extraembryonic endoderm. Five concentrations of all-trans retinoic acid (ATRA) between 0.001 and 10 µM were compared to time-matched 0.1% DMSO controls at three timepoints (6h, 96h, and 192h) in differentiating endoderm. Two biological replicates were used. Undifferentiated controls (not in DMSO) were also included in duplicate as internal controls for 6h, 96h, and 144h. This dataset is associated with the following publication: Saili, K., T. Antonijevic, T. Zurlinden, I. Shah, C. Deisenroth, and T. Knudsen. Molecular characterization of a toxicological tipping point during human stem cell differentiation. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 91(January 2020): 1-13, (2020).

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).

Data on hormone and chemical analysis is included for the effects of oxyfluorfen on thyroid hormones in the 4- and 8-day exposed juvenile rats. This dataset is associated with the following publication: Stoker, T., G. DeVane, A. Buckalew, J. Bailey, J. Ford, and A. Murr. Evaluation of the diphenyl herbicide, Oxyfluorfen, for effects on thyroid hormones in the juvenile rat.. Current Research in Toxicology. Elsevier B.V., Amsterdam, NETHERLANDS, 6: 100146, (2023).

This dataset includes the results of a long term adult female rat oral exposure to triclosan and includes hormone, estrous cyclicity, thyroid histology and liver gene expression data. This dataset is associated with the following publication: Louis, G., D. Hallinger, J. Braxton, A. Kamel, and T. Stoker. Effects of Chronic Exposure to Triclosan on Reproductive and Thyroid Endpoints in the Adult Wistar Female Rat. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. Taylor & Francis, Inc., Philadelphia, PA, USA, 236-249, (2017).

,Porcine reproductive and respiratory syndrome virus (PRRSV) causes respiratory disease in piglets and reproductive disease in sows. Piglet and fetal serum thyroid hormone (i.e., T3 and T4) levels decrease rapidly in response to PRRSV infection. However, the genetic control of T3 and T4 during infection is not completely understood. Our objective was to estimate genetic parameters and identify quantitative trait loci (QTL) for absolute T3 and/or T4 levels of piglets and fetuses challenged with PRRSV. Sera from 5-week-old pigs (N=1792) at 11 days post inoculation (DPI) with PRRSV were assayed for T3 levels (piglet_T3). Sera from fetuses (N=1267) at 12 or 21 days post maternal inoculation (DPMI) with PRRSV of sows (N=145) in late gestation were assayed for T3 (fetal_T3) and T4 (fetal_T4) levels. Animals were genotyped using 60K Illumina or 650K Affymetrix SNP panels. Heritabilities, phenotypic correlations, and genetic correlations were estimated using ASREML; genome wide association studies were performed for each trait separately using JWAS. All three traits were low to moderately heritable (10 to 16%). Phenotypic and genetic correlations of piglet_T3 levels with weight gain (0-42 DPI) were 0.26±0.03 and 0.67±0.14, respectively. Nine significant QTL were identified for piglet_T3, on Sus scrofa chromosomes (SSC) 3, 4, 5, 6, 7, 14, 15, and 17, and collectively explaining 30% of the genetic variation (GV), with the largest QTL identified on SSC5, explaining 15% of the GV. Three significant QTL were identified for fetal_T3 on SSC1 and SSC4, which collectively explained 10% of the GV. Five significant QTL were identified for fetal_T4 on SSC1, 6, 10, 13, and 15, which collectively explained 14% of the GV. Several putative immune-related candidate genes were identified, including CD247, IRF8, and MAPK8. Thyroid hormone levels following PRRSV infection were heritable and had positive genetic correlations with growth rate. Multiple QTL with moderate effects were identified for T3 and T4 levels during challenge with PRRSV and candidate genes were identified, including several immune-related genes. These results advance our understanding of growth effects of both piglet and fetal response to PRRSV infection, revealing factors associated with genomic control of host resilience.,Funded/supported by: US National Pork Board (NPB) (#07-233, #09-208, #10-033, #09-244, and #10-033); swine breeding companies Genus PIC plc, Newsham/Choice Genetics, FAST Genetics, Genetiporc, Genesus, Topigs Norsvin and PigGen Canada, Inc.; PRRS Coordinated Agricultural Project (PRRS-CAP); USDA-NIFA Award #2008-55620-19132; Genome Canada project #2209_F; USDA-NIFA Translational Genomics ( # 2013-68004-20362), USDA sponsored National Research Support Project 8 (NRSP-8) Swine Genome and Bioinformatics research programs; Kansas State University and USDA ARS (1245-32000-098 and 8042-32000-117); USDA ARS (# 8042–32000-102); SCINet project of the USDA ARS (0500-00093-001-00-D); USDA ARS Headquarters Postdoctoral Fellowship; Genome Canada (2014LSARP_8202); Genome Prairie (Project 346143); Genome Alberta.,,

- Observations of test subjects, - Body weight, organ/tissue weights - Biomarker data (oxidative DNA damage, thyroid hormones, corticosterone, gene expression) in various tissues - Residues as percent of administered dose - Tissues to plasma rations - Metabolites and ratios - Elimination half-lives