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膳食中2,3,7,8 - 四氯二苯并 - 对 - 二噁英的积累、组织分布及母体转移:对斑马鱼繁殖成功率的影响

Accumulation, tissue distribution, and maternal transfer of dietary 2,3,7,8,-tetrachlorodibenzo-p-dioxin: impacts on reproductive success of zebrafish.

作者信息

Heiden Tisha King, Hutz Reinhold J, Carvan Michael J

机构信息

Marine and Freshwater Biomedical Sciences Center, University of Wisconsin-Milwaukee Great Lakes WATER Institute, 53204, USA.

出版信息

Toxicol Sci. 2005 Oct;87(2):497-507. doi: 10.1093/toxsci/kfi201. Epub 2005 May 18.

Abstract

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a reproductive toxicant and endocrine disruptor in nearly all vertebrates; however, the mechanisms by which TCDD alters the reproductive system is not well understood. The zebrafish provides a powerful vertebrate model system to investigate molecular mechanisms by which TCDD affects the reproductive system, but little is known regarding reproductive toxic response of zebrafish following chronic, sublethal exposure to TCDD. Here we investigate the accumulation of TCDD in selected tissues of adult female zebrafish and maternal transfer to offspring following dietary exposure to TCDD (0.08-2.16 ng TCDD/fish/day). TCDD accumulated in tissues of zebrafish in a dose- and time-dependent manner, except for brain. Chronic dietary exposure resulting in the accumulation of 1.1-36 ng/g fish did not induce an overt toxic response or suppress spawning activity. The ovosomatic index was impacted with an accumulation of as little as 0.6 ng/g fish, and 10% of the females showed signs of ovarian necrosis following accumulation of approximately 3 ng/g TCDD. Offspring health was impacted with an accumulation of as little as 1.1 ng/g female; thus the lowest observed effect level (LOEL) for reproductive toxicity in female zebrafish is approximately 0.6-1.1 ng/g fish. Maternal transfer resulted in the accumulation of 0.094-1.2 ng/g, TCDD, which was sufficient to induce the typical endpoints of larval TCDD toxicity, commonly referred to as blue sac syndrome. This study provides the necessary framework to utilize the zebrafish model system for further investigations into the molecular mechanisms by which TCDD exerts its reproductive toxic responses.

摘要

2,3,7,8-四氯二苯并对二恶英(TCDD)在几乎所有脊椎动物中都是一种生殖毒物和内分泌干扰物;然而,TCDD改变生殖系统的机制尚未完全明确。斑马鱼提供了一个强大的脊椎动物模型系统,用于研究TCDD影响生殖系统的分子机制,但对于斑马鱼在长期、亚致死剂量接触TCDD后的生殖毒性反应知之甚少。在此,我们研究了成年雌性斑马鱼在经口暴露于TCDD(0.08 - 2.16纳克TCDD/鱼/天)后,TCDD在选定组织中的蓄积情况以及母体向后代的转移情况。TCDD在斑马鱼组织中的蓄积呈剂量和时间依赖性,但在脑中除外。长期经口暴露导致鱼体内蓄积1.1 - 36纳克/克,并未引发明显的毒性反应或抑制产卵活动。卵体指数在鱼体内TCDD蓄积量低至0.6纳克/克时就受到影响,在TCDD蓄积量约为3纳克/克时,10%的雌性出现卵巢坏死迹象。后代健康在雌性体内TCDD蓄积量低至1.1纳克/克时就受到影响;因此,雌性斑马鱼生殖毒性的最低观察到效应水平(LOEL)约为0.6 - 1.1纳克/克鱼。母体转移导致TCDD在后代体内蓄积量为0.094 - 1.2纳克/克,这足以引发幼体TCDD毒性的典型终点,通常称为蓝囊综合征。本研究提供了必要的框架,以便利用斑马鱼模型系统进一步研究TCDD发挥其生殖毒性反应的分子机制。

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