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在非洲爪蟾模型中评估丙环唑的发育生殖毒性和内分泌活性。

Developmental reproductive toxicity and endocrine activity of propiconazole in the Xenopus tropicalis model.

机构信息

Department of Environmental Toxicology, Uppsala University, Centre for Reproductive Biology in Uppsala (CRU), Sweden.

Department of Environmental Toxicology, Uppsala University, Centre for Reproductive Biology in Uppsala (CRU), Sweden.

出版信息

Sci Total Environ. 2021 Jan 20;753:141940. doi: 10.1016/j.scitotenv.2020.141940. Epub 2020 Aug 24.

DOI:10.1016/j.scitotenv.2020.141940
PMID:32890874
Abstract

Environmental pollutants and especially endocrine disrupting chemicals (EDCs) are implicated as one of the drivers of the amphibian declines. To advance the understanding of the risks of EDCs to amphibians, methods to determine endocrine-linked adverse effects are needed. The aims were to 1) develop a partial life-cycle assay with the model frog Xenopus tropicalis to determine endocrine perturbation and adverse developmental effects, and 2) determine effects of propiconazole in this assay. Propiconazole is a pesticide with multiple endocrine modes of action in vitro. Its potential endocrine activity and adverse effects in amphibians remain to be elucidated. Tadpoles were exposed to 0, 33 and 384 μg propiconazole/L during critical developmental windows until completed metamorphosis. At metamorphosis, a sub-sample of animals was analysed for endpoints for disruption of estrogen/androgen (sex ratio, brain aromatase activity) and thyroid pathways (time to metamorphosis). The remaining individuals were kept unexposed for 2 months post-metamorphosis to analyze effects on sexual development including gonadal and Müllerian duct maturity and gametogenesis. At metamorphosis, brain aromatase activity was significantly increased in the high-dose group compared to control. In both propiconazole groups, an increased proportion of individuals reached metamorphosis faster than the mean time for controls, suggesting a stimulatory effect on the thyroid system. At 2 months post-metamorphosis, testis size, sperm and Müllerian duct maturity were reduced in the low-dose males, and the liver somatic index in males was increased in both propiconazole groups, compared with controls. In conclusion, our results show that propiconazole exposure caused endocrine perturbations and subsequent hepatic and reproductive effects evident at puberty, indicating persistent disruption of metabolism and male reproductive function. Our findings advance the development of methodology to determine endocrine and adverse effects of EDCs. Moreover, they increase the understanding of endocrine perturbations and consequent risk of adverse effects of azoles in amphibians.

摘要

环境污染物,尤其是内分泌干扰化学物质(EDCs),被认为是导致两栖动物减少的因素之一。为了深入了解 EDC 对两栖动物的风险,需要确定与内分泌相关的不良影响的方法。本研究的目的是:1)建立一种具有模型蛙 Xenopus tropicalis 的部分生命周期测定法,以确定内分泌干扰和不良发育影响;2)确定在该测定法中丙环唑的作用。丙环唑是一种具有多种体外内分泌作用模式的农药。其在两栖动物中的潜在内分泌活性和不良影响仍有待阐明。在关键发育窗口期间,将蝌蚪暴露于 0、33 和 384μg/L 丙环唑/L 中,直到完全变态。在变态时,对动物的一个亚样本进行分析,以确定雌激素/雄激素(性别比例,大脑芳香酶活性)和甲状腺途径(变态时间)的干扰终点。其余个体在变态后 2 个月内保持未暴露状态,以分析对性发育的影响,包括性腺和 Müllerian 管成熟和配子发生。在变态时,与对照组相比,高剂量组的大脑芳香酶活性显著增加。在丙环唑组中,与对照组相比,有更多的个体在更快的时间内达到变态,这表明甲状腺系统受到了刺激。在变态后 2 个月时,与对照组相比,低剂量组雄性的睾丸大小、精子和 Müllerian 管成熟度降低,而丙环唑组雄性的肝脏体指数增加。总之,我们的研究结果表明,丙环唑暴露导致内分泌失调,并随后在青春期出现肝脏和生殖系统的不良影响,表明代谢和雄性生殖功能持续受到干扰。我们的研究结果推进了确定内分泌和 EDC 不良影响的方法的发展。此外,它们增加了对唑类化合物在两栖动物中的内分泌干扰和随后的不良影响风险的理解。

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