ArticleReproductive toxicology (Elmsford, N.Y.)2021
Combining in vitro assays and mathematical modelling to study developmental neurotoxicity induced by chemical mixtures.
Article in Reproductive toxicology (Elmsford, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 41 citations in OpenAlex.
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- Polychlorinated Biphenyls, Oxidative Stress, and Brain Health: Mechanistic Links to Neurodegenerative and Neurodevelopmental Diseases.Antioxidants (Basel, Switzerland) · 2026Review
- Advancing chemical mixture toxicity assessment using advanced in vitro NAMs: current status and future perspectives.Frontiers in toxicology · 2026Review
- Sex-specific impacts of prenatal bisphenol A exposure on genes associated with cortical development, social behaviors, and autism in the offspring's prefrontal cortex.Biology of sex differences · 2024Article
- Effect of bisphenol A on the neurological system: a review update.Archives of toxicology · 2024Review
- Wrangling Whole Mixtures Risk Assessment: Recent Advances in Determining Sufficient Similarity.Current opinion in toxicology · 2023Article
- New approach methodologies in human regulatory toxicology - Not if, but how and when!Environment international · 2023Review
- Assessment of neurotransmitter release in human iPSC-derived neuronal/glial cells: a missing in vitro assay for regulatory developmental neurotoxicity testing.Reproductive toxicology (Elmsford, N.Y.) · 2023Article
- Prediction ofFrontiers in pharmacology · 2023Article
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- Vesicular Glutamate Release from Feeder-FreehiPSC-Derived Neurons.International journal of molecular sciences · 2022Article
- Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation: Possible implications for SARS-CoV-2 impact on brain development.Reproductive toxicology (Elmsford, N.Y.) · 2022Article
- Studying metabolism with multi-organ chips: new tools for disease modelling, pharmacokinetics and pharmacodynamics.Open biology · 2022Review
- Roadbumps at the Crossroads of Integrating Behavioral andFrontiers in toxicology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prenatal and postnatal co-exposure to multiple chemicals at the same time may have deleterious effects on the developing nervous system. We previously showed that chemicals acting through similar mode of action (MoA) and grouped based on perturbation of brain derived neurotrophic factor (BDNF), induced greater neurotoxic effects on human induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes compared to chemicals with dissimilar MoA. Here we assessed the effects of repeated dose (14 days) treatments with mixtures containing the six chemicals tested in our previous study (Bisphenol A, Chlorpyrifos, Lead(II) chloride, Methylmercury chloride, PCB138 and Valproic acid) along with 2,2'4,4'-tetrabromodiphenyl ether (BDE47), Ethanol, Vinclozolin and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)), on hiPSC-derived neural stem cells undergoing differentiation toward mixed neurons/astrocytes up to 21 days. Similar MoA chemicals in mixtures caused an increase of BDNF levels and neurite outgrowth, and a decrease of synapse formation, which led to inhibition of electrical activity. Perturbations of these endpoints are described as common key events in adverse outcome pathways (AOPs) specific for DNT. When compared with mixtures tested in our previous study, adding similarly acting chemicals (BDE47 and EtOH) to the mixture resulted in a stronger downregulation of synapses. A synergistic effect on some synaptogenesis-related features (PSD95 in particular) was hypothesized upon treatment with tested mixtures, as indicated by mathematical modelling. Our findings confirm that the use of human iPSC-derived mixed neuronal/glial models applied to a battery of in vitro assays anchored to key events in DNT AOP networks, combined with mathematical modelling, is a suitable testing strategy to assess in vitro DNT induced by chemical mixtures.
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