Pregnane X receptor attenuates gold nanoparticles’ toxicity through accelerating zebrafish embryo hatching

IF 4.1 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology Pub Date : 2025-05-04 DOI:10.1016/j.aquatox.2025.107399

Jia Hu , Jingjing Tian , Pai Liu , Qian Zhang , Ningyao Li , Jian Yin

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引用次数: 0

Abstract

It is well known that fish embryos are vulnerable to waterborne nanoparticles (NPs), with delayed hatching being the most common and sensitive endpoint. Up-regulation of hatching enzymes has been believed to be an important detoxification mechanism for NPs, but the inner mechanism for such phenomena has been seldom investigated. This study aimed to investigate the role of pregnane X receptor (Pxr) in maintaining the robustness of embryo hatching after treatment with gold nanoparticles (AuNPs, 4 and 82 nm). For this purpose, embryos from mating of 6-month-old wild-type (WT) AB strain zebrafish (Danio rerio, 3∼4-cm-length) were treated with AuNPs since 4 h post-fertilization (hpf). It was found that both AuNPs significantly inhibited embryo hatching after 52-h treatment, with Au-4 being more toxic at the same mass concentrations. At non-toxic concentrations and median effective concentrations (EC₅₀) of delayed hatching, both AuNPs induced the mRNA expression of HEs and Pxr at 48 hpf, and Au-4 seemed to be more effective. The induction extents of HEs by AuNPs decreased when Pxr was knocked out or inhibited, indicating the role of Pxr in such process. Additionally, knockout/inhibition of Pxr significantly delayed the hatching of embryos at 56 hpf, and activation of Pxr accelerated the process at moderate concentrations. Such phenomena correlated well with the alterations in the mRNA expression and activities of HEs, indicating a fact that AuNPs activated Pxr and up-regulated HEs, which helped the detoxification of AuNPs. RNA-sequencing analysis of WT and pxr-deficient embryos at 24 hpf confirmed the alteration of he1.1&1.2. In addition, Pxr influenced mRNA encoding muscle development (muscle system process and striated muscle tissue development) and energy metabolism (carbohydrate metabolic process and ATP metabolic process), which were related to the motility of embryos and determined the hatching speed. Such function was confirmed by the reduced locomotor activity of pxr-deficient larvae at 120 hpf. Overall, these results suggested a novel role of Pxr in promoting the hatching of zebrafish embryos, which contributed to the detoxification of AuNPs.

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孕烷X受体通过加速斑马鱼胚胎孵化来减弱金纳米颗粒的毒性

众所周知，鱼类胚胎容易受到水生纳米颗粒（NPs）的影响，延迟孵化是最常见和最敏感的终点。孵化酶的上调被认为是NPs解毒的重要机制，但其内部机制却很少被研究。本研究旨在探讨孕X受体（Pxr）在纳米金（AuNPs， 4和82 nm）处理后维持胚胎孵化稳健性的作用。为此，6月龄野生型（WT） AB型斑马鱼（Danio rerio， 3 ~ 4 cm长）的交配胚胎在受精后4小时（hpf）用AuNPs处理。结果发现，处理52 h后，两种AuNPs均能显著抑制胚胎孵化，且相同质量浓度下Au-4的毒性更大。在延迟孵化的无毒浓度和中位有效浓度（EC50）下，两种AuNPs均能诱导48 hpf的HEs和Pxr mRNA表达，且Au-4似乎更有效。当Pxr被敲除或抑制时，AuNPs对HEs的诱导程度降低，说明Pxr在这一过程中发挥了作用。此外，Pxr的敲除/抑制显著延迟胚胎在56 hpf时的孵化，而Pxr的激活在中等浓度下加速了这一过程。这种现象与HEs mRNA表达和活性的改变有良好的相关性，说明AuNPs激活Pxr，上调HEs，有助于AuNPs的解毒。在24 hpf时对WT和pxr缺陷胚胎的rna测序分析证实了he1.1&；1.2的改变。此外，Pxr影响了肌肉发育（肌肉系统过程和横纹肌组织发育）和能量代谢（碳水化合物代谢过程和ATP代谢过程）的mRNA编码，这些mRNA与胚胎的运动能力有关，并决定了孵化速度。pxr缺陷幼虫在120 hpf时运动能力下降，证实了这种功能。总之，这些结果表明Pxr在促进斑马鱼胚胎的孵化中发挥了新的作用，这有助于aunp的解毒。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Aquatic Toxicology 环境科学-毒理学

CiteScore

7.10

自引率

4.40%

发文量

250

审稿时长

56 days

期刊介绍： Aquatic Toxicology publishes significant contributions that increase the understanding of the impact of harmful substances (including natural and synthetic chemicals) on aquatic organisms and ecosystems. Aquatic Toxicology considers both laboratory and field studies with a focus on marine/ freshwater environments. We strive to attract high quality original scientific papers, critical reviews and expert opinion papers in the following areas: Effects of harmful substances on molecular, cellular, sub-organismal, organismal, population, community, and ecosystem level; Toxic Mechanisms; Genetic disturbances, transgenerational effects, behavioral and adaptive responses; Impacts of harmful substances on structure, function of and services provided by aquatic ecosystems; Mixture toxicity assessment; Statistical approaches to predict exposure to and hazards of contaminants The journal also considers manuscripts in other areas, such as the development of innovative concepts, approaches, and methodologies, which promote the wider application of toxicological datasets to the protection of aquatic environments and inform ecological risk assessments and decision making by relevant authorities.