Quantitative prediction of zebrafish reproductive impairment via androgen receptor-driven adverse outcome pathway

IF 4.6 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology Pub Date : 2026-03-01 Epub Date: 2026-01-16 DOI:10.1016/j.aquatox.2026.107720

Xuan Liu , Hongxia Yu , You Song , Wei Shi , Hongling Liu

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引用次数: 0

Abstract

Exogenous androgenic contaminants have long been of concern and are associated with reproductive impairment in fish. Although Toxcast has screened a large number of compounds using in vitro testing, it is challenging to conduct high-throughput tests for complex effects in vivo and to assess apical endpoints such as reproduction further quantitatively. Therefore, we developed a quantitative prediction method for reproductive dysfunction in zebrafish based on the adverse outcome pathway (AOP) framework. We carried out in vitro androgen activity tests for 16 compounds and a 21-day exposure experiment of androgen receptor (AR) agonism reference chemical 17β-trenbolone (TB) in zebrafish. The results revealed that TB mainly affected the levels of 11-ketotestosterone, estradiol, and vitellogenin in females by mediating AR, and caused abnormal ovarian development and fecundity decline. Then, AOP leading to reproductive dysfunction in female zebrafish (ZqAOP) was assembled and quantified, and it was validated to determine the potential and reliability for chemical extrapolation. Finally, the ZqAOP model was applied for predicting the potential reproductive impairments of eight compounds in environmental concentrations and global surface water samples with AR activity. This study provides a new insight into screening and assessing large numbers of chemicals with potential endocrine-disrupting effects.

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通过雄激素受体驱动的不良后果途径定量预测斑马鱼生殖功能障碍

外源性雄激素污染物长期以来一直受到关注，并与鱼类生殖功能障碍有关。尽管Toxcast已经使用体外测试筛选了大量化合物，但在体内对复杂效应进行高通量测试以及进一步定量评估生殖等根尖终点是具有挑战性的。因此，我们建立了一种基于不良结果通路（adverse outcome pathway， AOP）框架的斑马鱼生殖功能障碍定量预测方法。我们对16种化合物进行了体外雄激素活性测试，并对斑马鱼进行了雄激素受体（AR）激动剂对照物17β-trenbolone （TB）的21天暴露实验。结果表明，TB主要通过介导AR影响女性体内11-酮睾酮、雌二醇和卵黄原素水平，导致卵巢发育异常和生殖力下降。然后，对导致雌性斑马鱼生殖功能障碍的AOP （ZqAOP）进行组装和量化，并对其进行验证，以确定化学外推的潜力和可靠性。最后，应用ZqAOP模型预测了8种化合物在具有AR活性的环境浓度和全球地表水样品中的潜在生殖损伤。这项研究为筛选和评估大量具有潜在内分泌干扰作用的化学物质提供了新的见解。

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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.