ArticleNeurotoxicology and teratology2012
Developmental neurotoxicity of organophosphates targets cell cycle and apoptosis, revealed by transcriptional profiles in vivo and in vitro.
Article in Neurotoxicology and teratology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Evaluation of developmental toxicity of chlorpyrifos through new approach methodologies: a systematic review.Archives of toxicology · 2025Pooled it
- Evaluation of an Integrated In Silico-In Vitro Pipeline for Predicting Mitochondrial Complex I-Mediated Neurotoxicity of Chlorpyrifos.Neurotoxicity research · 2026Article
- Impact of glyphosate-based herbicide exposure through maternal milk on offspring's antioxidant status, neurodevelopment, and behavior.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Effects of the nerve agent VX on hiPSC-derived motor neurons.Archives of toxicology · 2024Article
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- Developmental Neurotoxicity of Fipronil and Rotenone on a Human Neuronal In Vitro Test System.Neurotoxicity research · 2021Article
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- Gestational and Lactational Exposure to Malathion Affects Antioxidant Status and Neurobehavior in Mice Pups and Offspring.Journal of molecular neuroscience : MN · 2019Article
- Resveratrol Prevents the Cellular Damages Induced by Monocrotophos via PI3K Signaling Pathway in Human Cord Blood Mesenchymal Stem Cells.Molecular neurobiology · 2018Article
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- Flame retardants and their metabolites in the homes and urine of pregnant women residing in California (the CHAMACOS cohort).Chemosphere · 2017Article
- Developmental neurotoxicity of succeeding generations of insecticides.Environment international · 2017Review
- Diverse neurotoxicants target the differentiation of embryonic neural stem cells into neuronal and glial phenotypes.Toxicology · 2016Article
- Adverse Associations of both Prenatal and Postnatal Exposure to Organophosphorous Pesticides with Infant Neurodevelopment in an Agricultural Area of Jiangsu Province, China.Environmental health perspectives · 2016Article
- Differential epigenetic effects of chlorpyrifos and arsenic in proliferating and differentiating human neural progenitor cells.Reproductive toxicology (Elmsford, N.Y.) · 2016Article
- AnToxicology research · 2016Article
- Lactobacillus Casei Decreases Organophosphorus Pesticide Diazinon Cytotoxicity in Human HUVEC Cell Line.Advanced pharmaceutical bulletin · 2016Article
- The NIEHS Superfund Research Program: 25 Years of Translational Research for Public Health.Environmental health perspectives · 2015Article
- Effects of maternal chlorpyrifos diet on social investigation and brain neuroendocrine markers in the offspring - a mouse study.Environmental health : a global access science source · 2015Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Developmental organophosphate exposure reduces the numbers of neural cells, contributing to neurobehavioral deficits. We administered chlorpyrifos or diazinon to newborn rats on postnatal days 1-4, in doses straddling the threshold for barely-detectable cholinesterase inhibition, and evaluated gene expression in the cell cycle and apoptosis pathways on postnatal day 5. Both organophosphates evoked transcriptional changes in 20-25% of the genes in each category; chlorpyrifos and diazinon targeted the same genes, with similar magnitudes of change, as evidenced by high concordance. Furthermore, the same effects were obtained with doses above or below the threshold for cholinesterase inhibition, indicating a mechanism unrelated to anticholinesterase actions. We then evaluated the effects of chlorpyrifos in undifferentiated and differentiating PC12 cells and found even greater targeting of cell cycle and apoptosis genes, affecting up to 40% of all genes in the pathways. Notably, the genes affected in undifferentiated cells were not concordant with those in differentiating cells, pointing to dissimilar outcomes dependent on developmental stage. The in vitro model successfully identified 60-70% of the genes affected by chlorpyrifos in vivo, indicating that the effects are exerted directly on developing neural cells. Our results show that organophosphates target the genes regulating the cell cycle and apoptosis in the developing brain and in neuronotypic cells in culture, with the pattern of vulnerability dependent on the specific stage of development. Equally important, these effects do not reflect actions on cholinesterase and operate at exposures below the threshold for any detectable inhibition of this enzyme.
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Registered trials
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