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[内分泌干扰物:流行病学研究证据促使对模型系统进行批判性审视]

[Endocrine disruptors : Evidence from epidemiological studies necessitates a critical review of model systems].

作者信息

Hoffmann M, Gebauer S, Nüchter M, Baber R, Ried J, von Bergen M, Kiess W

机构信息

Klinik und Poliklinik für Kinder- und Jugendmedizin, Zentrum für pädiatrische Forschung, Universitätsklinikum Leipzig AöR, Liebigstraße 20a, 04103, Leipzig, Deutschland.

LIFE - Leipziger Forschungszentrum für Zivilisationserkrankungen, Universität Leipzig, Leipzig, Deutschland.

出版信息

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2017 Jun;60(6):640-648. doi: 10.1007/s00103-017-2551-8.

DOI:10.1007/s00103-017-2551-8
PMID:28447138
Abstract

Endocrine disruptive chemicals (EDCs) cause adverse health effects through interaction with endocrine systems. They are classified by chemical structure, effects on specific endocrine systems, bioaccumulation, persistence in the environment, or clinically observable effects. For research of the complex mechanisms of action in the human body, only in vitro model systems have so far been available, that have insufficient high-throughput capacity, which makes risk evaluation more difficult. In addition, in industrial nations, living people are often exposed to mixtures of substances, with various effects. The clinical importance of epigenetic changes caused by the action of EDCs during vulnerable phases of development is currently unclear. Epidemiological studies are criticized because reproducibility is not always guaranteed. Nevertheless, they remain the method of choice for the development and analysis of suitable model systems. Positive associations, in spite of sometimes conflicting results, are key in the selection of factors that can then be analysed in model systems in an unbiased way. This article depicts the mainly positive epidemiological findings for EDC-caused effects in the fields of growth and metabolism, neurocognitive development and sexual development and reproduction. As a result, there is a need for closer linkage between epidemiological studies and mechanistic research into model systems, especially focusing on the interaction of different EDCs and the consequences of prenatal and early life exposure.

摘要

内分泌干扰化学物质(EDCs)通过与内分泌系统相互作用对健康产生不良影响。它们可根据化学结构、对特定内分泌系统的影响、生物累积性、在环境中的持久性或临床可观察到的影响进行分类。对于人体复杂作用机制的研究,目前只有体外模型系统可用,但这些系统的高通量能力不足,这使得风险评估更加困难。此外,在工业化国家,人们经常接触具有各种影响的物质混合物。目前尚不清楚在发育的脆弱阶段,EDCs作用引起的表观遗传变化的临床重要性。流行病学研究受到批评,因为其可重复性并非总能得到保证。尽管如此,它们仍然是开发和分析合适模型系统的首选方法。尽管有时结果相互矛盾,但阳性关联是选择能够随后在模型系统中以无偏方式进行分析的因素的关键。本文描述了在生长与代谢、神经认知发育以及性发育与生殖领域中,关于EDCs所致影响的主要阳性流行病学研究结果。因此,需要在流行病学研究与模型系统的机制研究之间建立更紧密的联系,尤其要关注不同EDCs之间的相互作用以及产前和生命早期暴露的后果。

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