EFFECTOF ENVIRONMENTAL CHEMICALS ON GUT MICROBIOME
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB12306 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR1231640.fastq.gz | Fastqsanger.gz | |||
| ERR1231650.fastq.gz | Fastqsanger.gz | |||
| ERR1231660.fastq.gz | Fastqsanger.gz | |||
| ERR1231670.fastq.gz | Fastqsanger.gz |
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Project description:Exposure to environmental chemicals can impair neurodevelopment, and oligodendrocytes may be particularly vulnerable as their development extends from gestation into adulthood. However, few environmental chemicals have been assessed for potential risks to oligodendrocytes. Here, using a high-throughput developmental screen in cultured cells, we identified environmental chemicals in two classes that disrupt oligodendrocyte development through distinct mechanisms. Quaternary compounds, ubiquitous in disinfecting agents and personal care products, were potently and selectively cytotoxic to developing oligodendrocytes, whereas organophosphate flame retardants, commonly found in household items such as furniture and electronics, prematurely arrested oligodendrocyte maturation. Chemicals from each class impaired oligodendrocyte development postnatally in mice and in a human 3D organoid model of prenatal cortical development. Analysis of epidemiological data showed that adverse neurodevelopmental outcomes were associated with childhood exposure to the top organophosphate flame retardant identified by our screen. This work identifies toxicological vulnerabilities for oligodendrocyte development and highlights the need for deeper scrutiny of these compounds’ impacts on human health.
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Project description:Exposure to environmental chemicals can impair neurodevelopment. Oligodendrocytes that wrap around axons to boost neurotransmission may be particularly vulnerable to chemical toxicity as they develop throughout fetal development and into adulthood. However, few environmental chemicals have been assessed for potential risks to oligodendrocyte development. Here, we utilized a high-throughput developmental screen and human cortical brain organoids, which revealed environmental chemicals in two classes that disrupt oligodendrocyte development. Quaternary compounds, ubiquitous in disinfecting agents, hair conditioners, and fabric softeners, were potently and selectively cytotoxic to developing oligodendrocytes through activation of the integrated stress response. Organophosphate flame retardants, commonly found in household items such as furniture and electronics, were non-cytotoxic but prematurely arrested oligodendrocyte maturation. Chemicals from each of the two classes impaired human oligodendrocyte development in a 3D organoid model of prenatal cortical development. In analysis of epidemiological data from the CDC’s National Health and Nutrition Examination Survey, adverse neurodevelopmental outcomes were associated with childhood exposure to the top organophosphate flame retardant identified in our oligodendrocyte toxicity platform. Collectively, our work identifies toxicological vulnerabilities specific to oligodendrocyte development and highlights common household chemicals with high exposure risk to children that warrant deeper scrutiny for their impact on human health.
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Project description:Environmental chemicals such as bisphenol A (BPA) are thought to contribute to carcinogenesis through their endocrine-disrupting effects. However BPA replacement chemicals are structurally similar, and little data exist describing their effects on the human body and environment. We established non-malignant human mammary organoid cultures to investigate the effects of BPA replacement chemicals on organoid morphology and protein abundance. At low-nanomolar doses, replacement chemicals, in particular BPS, induced branching and disrupted the organized mammary organoid architecture. BPS exposure likely alters mammary cell-type proportions and induces branching of predominately myoepithelial cells. Treatment with different replacement chemicals resulted in distinct proteomic changes. BPS exposure induced Cdc42-interacting protein 4 (CIP4), a protein known to support invadopodia formation and mesenchymal phenotypes. Our study provides evidence that replacement bisphenols have pro-tumorigenic effects on mammary morphology and the proteome, highlighting the necessity of comprehensive studies to evaluate the potential harm of replacement chemicals.
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