ArticleToxicological sciences : an official journal of the Society of Toxicology2018
Developmental Thyroid Hormone Insufficiency Induces a Cortical Brain Malformation and Learning Impairments: A Cross-Fostering Study.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 54 citations in OpenAlex.
- Maternal exposure to the thyroperoxidase-inhibiting pesticide amitrole induces hypothyroidism and developmental neurotoxicity in the rat brain.Frontiers in endocrinology · 2026Article
- Evaluations of Sex Differences in Dosimetry in Rats Following Perfluorohexanesulfonamide (PFHxSA) Oral Exposure.Toxics · 2025Article
- Key Messages of the Iodine Deficiency Working Group (AKJ): Maternal Hypothyroxinemia Due to Iodine Deficiency and Endocrine Disruptors as Risks for Child Neurocognitive Development.Geburtshilfe und Frauenheilkunde · 2025Article
- Evaluating the performance of multi-omics integration: a thyroid toxicity case study.Archives of toxicology · 2025Article
- Mild Gestational Hypothyroidism in Mice Has Transient Developmental Effects and Long-Term Consequences on Neuroendocrine Systems.Thyroid : official journal of the American Thyroid Association · 2025Article
- Review
- Long-chain perfluoroalkylether carboxylic acids PFO5DoA and PFO4DA alter glucose, bile acid, and thyroid hormone homeostasis in fetal rats from 5-day maternal oral exposure.Environmental research · 2024Article
- Article
- Optimal testing time for cerebral heterotopia formation in the rat comparative thyroid assay, a downstream indicator for perinatal thyroid hormone insufficiency.Journal of toxicologic pathology · 2024Article
- The pollutant perfluorohexane sulfonate (PFHxS) reduces serum thyroxine but does not alter thyroid action in the postnatal rat brain.Environment international · 2024Article
- Bypassing the brain barriers: upregulation of serum miR-495 and miR-543-3p reflects thyroid-mediated developmental neurotoxicity in the rat.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Ammonium perchlorate: serum dosimetry, neurotoxicity, and resilience of the neonatal rat thyroid system.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- A 2024 inventory of test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment.Open research Europe · 2024Review
- Prenatal test cohort of a modified rat comparative thyroid assay adding brain thyroid hormone measurements and histology but lowering group size appears able to detect disruption by sodium phenobarbital.Current research in toxicology · 2024Article
- Structural Malformations in the Neonatal Rat Brain Accompany Developmental Exposure to Ammonium Perchlorate.Toxics · 2023Article
- Article
- Cross-species applicability of an adverse outcome pathway network for thyroid hormone system disruption.Toxicological sciences : an official journal of the Society of Toxicology · 2023Review
- Local Thyroid Hormone Action in Brain Development.International journal of molecular sciences · 2023Review
- Reducing uncertainties in quantitative adverse outcome pathways by analysis of thyroid hormone in the neonatal rat brain.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Iodine Deficiency, Maternal Hypothyroxinemia and Endocrine Disrupters Affecting Fetal Brain Development: A Scoping Review.Nutrients · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Thyroid hormones (THs) are essential for brain development, but few rodent models exist that link TH inefficiency to apical neurodevelopmental endpoints. We have previously described a structural anomaly, a heterotopia, in the brains of rats treated in utero with propylthiouracil (PTU). However, how the timing of an exposure relates to this birth defect is unknown. This study seeks to understand how various temporal treatments of the mother relates to TH insufficiency and adverse neurodevelopment of the offspring. Pregnant rats were exposed to PTU (0 or 3 ppm) through the drinking water from gestational day 6 until postnatal day (PN) 14. On PN2 a subset of pups was cross-fostered to a dam of the opposite treatment, to create 4 conditions: pups exposed to PTU prenatally, postnatally, during both periods, or not at all (control). Both PTU and TH concentrations were characterized in the mother and offspring over time, to capture the dynamics of a developmental xenobiotic exposure. Brains of offspring were examined for heterotopia presence and severity, and adult littermates were assessed for memory impairments. Heterotopia were observed under conditions of prenatal exposure, and its severity increased in animals in the most prolonged exposure group. This malformation was also permanent, but not sex biased. In contrast, behavioral impairments were limited to males, and only in animals exposed to PTU during both the gestational and postnatal periods. This suggests a distinct TH-dependent etiology for both phenotypes, and illustrates how timing of hypothyroxinemia can induce abnormal brain structure and function.
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