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Synergistic transgenerational reproductive toxicity of polystyrene nanoplastics and butylparaben at NOAEL levels via SET-2–mediated H3K4me3 modification in Caenorhabditis elegans
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Researchers found that co-exposure to polystyrene nanoplastics and butylparaben at individually non-toxic doses produced synergistic reproductive toxicity across multiple generations in the model organism C. elegans. The combined exposure caused transgenerational damage through epigenetic modifications involving histone methylation. The study suggests that mixtures of nanoplastics and common consumer product chemicals may pose hidden reproductive risks even when each substance alone appears safe.
Emerging contaminants such as polystyrene nanoplastics (PS-NPs) and butylparaben (BuP) frequently co-occur in surface waters and sediments, raising concerns about mixture risks at environmentally relevant doses. Although each compound is non-effective at its individual no-observed-adverse-effect level (NOAEL), their joint long-term impacts remain insufficiently defined. Here, we used Caenorhabditis elegans as a multigenerational in vivo model to test whether maternal co-exposure to PS-NPs and BuP at NOAELs induces heritable reproductive toxicity. Maternal co-exposure reduced reproductive outcome and increased germline apoptosis across four generations. Bliss independence analysis indicated a synergistic interaction. Mechanistically, co-exposure elevated intestinal reactive oxygen species (ROS) and increased embryonic histone H3K4 trimethylation (H3K4me3). Notably, reproductive impairments and H3K4me3 elevation were absent in set-2 mutants, indicating that SET-2-mediated H3K4 trimethylation is essential for transmitting transgenerational toxicity. Our findings underscore the limitations of single compound NOAEL-based assessments and support incorporating epigenetic biomarkers and transgenerational endpoints into chemical risk evaluation frameworks.
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Photoaged Polystyrene Nanoplastics Result in Transgenerational Reproductive Toxicity Associated with the Methylation of Histone H3K4 and H3K9 in Caenorhabditis elegans
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When roundworms were exposed to sun-aged polystyrene nanoplastics at environmentally relevant levels, the reproductive damage passed down to unexposed future generations through changes in gene-regulating chemical marks called histone methylation. Sun-aged nanoplastics caused more severe fertility problems than fresh ones, and these effects persisted for two generations after exposure stopped. This study is alarming because it shows nanoplastic exposure could cause hereditary reproductive harm without changing DNA itself.
Transgenerational response of germline histone acetyltransferases and deacetylases to nanoplastics at predicted environmental doses in Caenorhabditis elegans
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Researchers showed that polystyrene nanoplastics at environmentally predicted doses suppress germline histone acetyltransferases and deacetylases in C. elegans, and that silencing these chromatin-regulating enzymes worsened toxicity across multiple generations by dysregulating signaling ligands — identifying histone deacetylase inhibition as the molecular initiating event in an epigenetic adverse outcome pathway.
Sulfonate-Modified Polystyrene Nanoparticle at Precited Environmental Concentrations Induces Transgenerational Toxicity Associated with Increase in Germline Notch Signal of Caenorhabditis elegans
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Researchers exposed tiny roundworms to sulfonate-modified nanoplastics at low, environmentally realistic concentrations and observed harmful effects that persisted across multiple generations. The nanoplastics activated the Notch signaling pathway in reproductive cells, leading to reduced movement and shortened lifespan in unexposed offspring. This suggests nanoplastic exposure could cause lasting biological changes passed down through generations.
Polystyrene nanoplastics induced transgenerational reproductive toxicity in Caenorhabditis elegans through enhanced DNA damage accompanied by DNA repair inhibition
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Researchers exposed roundworms (C. elegans) to polystyrene nanoplastics at environmentally relevant concentrations and found that reproductive harm persisted across multiple generations, even after exposure stopped. The nanoplastics caused DNA damage while simultaneously suppressing the organisms' DNA repair mechanisms, creating a compounding effect. The study suggests that nanoplastic exposure may have lasting consequences that are passed down through generations, amplifying harm beyond the originally exposed organisms.
Transgenerational Response of Germline Nuclear Hormone Receptor Genes to Nanoplastics at Predicted Environmental Doses in Caenorhabditis elegans
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Exposure to very low doses of polystyrene nanoplastics in roundworms caused reproductive and developmental problems that persisted across multiple generations through changes in nuclear hormone receptor genes. These receptors control important signaling pathways, and their disruption altered the expression of insulin and other growth signals in offspring that were never directly exposed to nanoplastics. This demonstrates that nanoplastic effects can be inherited through epigenetic mechanisms even at doses found in the environment.
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