Endocrine effects of Imazalil on aromatase expression, vitellogenesis and ovarian histology using cyp19a1a-eGFP-casper transgenic zebrafish

IF 4.3 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology Pub Date : 2025-09-17 DOI:10.1016/j.aquatox.2025.107580

Julie De Oliveira , Tu-Ky Ly , Edith Chadili , Violette Thermes , Antoine Mergot , Benjamin Piccini , Olivier Palluel , Hélène Budzinski , Karyn Le Menach , Patrick Pardon , Rémy Beaudouin , Xavier Cousin , François Brion , Nathalie Hinfray

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引用次数: 0

Abstract

Considering the hazards and risks posed by endocrine disrupting chemicals (EDC) to organisms, there is a need to study their effects. To that end, transgenic fish are powerful models that can provide mechanistic information regarding the endocrine activity of test chemicals. In this study, we used a newly developed transgenic zebrafish line (cyp19a1a-eGFP-casper) in the OECD 21-day fish assay (OECD TG 230) to provide additional mechanistic insight on Imazalil (IMZ; 1.9; 9.9 and 140.7 µg/L). After 21 days of exposure to IMZ, the circulating concentrations of 17-β-estradiol (E2) and vitellogenin decreased in females, reflecting the aromatase activities inhibition. Exposure to 140.7 µg/L of IMZ for 21 days also resulted in a change in the proportion of the different oocyte stages in the ovaries, with an accumulation of large oocytes in exposed females. In addition to the classical endpoints, in vivo GFP fluorescence was quantified in the ovaries during the time course of the exposure to follow gonadal aromatase expression. After seven days of exposure, ovarian aromatase expression increased in females exposed to medium and high concentrations of IMZ, persisting over the 21-day of exposure in fish from the highest concentration group and reflecting a compensatory response to the aromatase enzymatic activities inhibition. Results from the present study provided valuable information on the mode of action and the effects of IMZ in zebrafish. Transgenic zebrafish exposure to IMZ caused a cascade of responses consistent with effects reported for wild-type fish exposed to azole fungicides, both qualitatively and quantitatively. The cyp19a1a-eGFP(-casper) transgenic zebrafish lines, allowed in vivo monitoring of gonadal aromatase expression in a time- and concentration-dependent manner thereby demonstrating their relevance to provide complementary mechanistic information on aromatase in regulatory assays such as OECD TG 230.

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依马唑利对cyp19a1a-eGFP-casper转基因斑马鱼芳香化酶表达、卵黄形成和卵巢组织学的内分泌影响

考虑到内分泌干扰物（EDC）对生物体的危害和风险，有必要研究其影响。为此，转基因鱼是强有力的模型，可以提供有关测试化学品内分泌活动的机制信息。在这项研究中，我们使用了一种新开发的转基因斑马鱼系（cyp19a1a-eGFP-casper）进行了经合组织21天鱼类试验（经合组织TG 230），以进一步了解Imazalil （IMZ; 1.9, 9.9和140.7µg/L）的作用机制。暴露于IMZ 21天后，雌性体内17-β-雌二醇（E2）和卵黄原素的循环浓度下降，反映出芳香酶活性受到抑制。暴露于140.7µg/L的IMZ中21天也导致卵巢中不同阶段的卵母细胞比例发生变化，暴露的雌性卵母细胞积累较大。除了经典的终点外，在暴露的时间过程中，对卵巢中的体内GFP荧光进行量化，以跟踪性腺芳香酶的表达。暴露7天后，暴露于中高浓度IMZ的雌性卵巢芳香酶表达增加，并在暴露于高浓度组的鱼类中持续了21天，反映了对芳香酶酶活性抑制的代偿反应。本研究的结果为IMZ对斑马鱼的作用方式和影响提供了有价值的信息。转基因斑马鱼暴露于IMZ引起的级联反应，在定性和定量上与野生型鱼暴露于唑类杀菌剂的效应一致。cyp19a1a-eGFP（-casper）转基因斑马鱼株系允许以时间和浓度依赖的方式在体内监测性腺芳香化酶的表达，从而证明它们在经合组织TG 230等调节试验中提供芳香化酶的补充机制信息的相关性。

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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.