关键词: NHRs nanoplastics nematode transgenerational toxicity

来  源:   DOI:10.3390/toxics12060420   PDF(Pubmed)

Abstract:
Transgenerational nanoplastic toxicity could be detected in Caenorhabditis elegans after exposure at the parental generation (P0-G); however, the underlying mechanisms remain largely unclear. We aimed to examine the role of germline nuclear hormone receptors (NHRs) in controlling the transgenerational toxicity of polystyrene nanoparticles (PS-NPs) based on gene expression screening and functional analysis. Among germline NHR genes, daf-12, nhr-14, and nhr-47 expressions were increased and nhr-12 expression was decreased by PS-NPs (1 and 10 μg/L). Transgenerational alterations in expressions of these four NHR genes were also induced by PS-NPs (1 and 10 μg/L). RNAi of daf-12, nhr-14, and nhr-47 caused resistance, whereas RNAi of nhr-12 conferred susceptibility to transgenerational PS-NP toxicity. After PS-NP exposure, expressions of ins-3, daf-28, and ins-39 encoding insulin ligands, efn-3 encoding Ephrin ligand, and lin-44 encoding Wnt ligand, as well as expressions of their receptor genes (daf-2, vab-1, and/or mig-1), were dysregulated by the RNAi of daf-12, nhr-14, nhr-47, and nhr-12. Therefore, alteration in certain germline NHRs could mediate the induction of transgenerational nanoplastic toxicity by affecting secreted ligands and their receptors in the offspring of exposed organisms.
摘要:
在亲代(P0-G)暴露后,可以在秀丽隐杆线虫中检测到跨代纳米塑料毒性;然而,潜在的机制在很大程度上仍不清楚.我们旨在基于基因表达筛选和功能分析,研究种系核激素受体(NHR)在控制聚苯乙烯纳米颗粒(PS-NP)的跨代毒性中的作用。在种系NHR基因中,PS-NP(1和10μg/L)增加了daf-12,nhr-14和nhr-47的表达,而nhr-12的表达降低。PS-NP(1和10μg/L)也诱导了这四种NHR基因表达的代际变化。daf-12,nhr-14和nhr-47的RNAi引起抗性,而nhr-12的RNAi赋予了对跨代PS-NP毒性的易感性。PS-NP暴露后,编码胰岛素配体的ins-3,daf-28和ins-39的表达,efn-3编码Ephrin配体,和lin-44编码Wnt配体,以及它们的受体基因(daf-2,vab-1和/或mig-1)的表达,daf-12、nhr-14、nhr-47和nhr-12的RNAi失调。因此,某些种系NHRs的改变可以通过影响暴露生物后代的分泌配体及其受体来介导跨代纳米塑料毒性的诱导。
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