Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity.

Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity.
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大鼠睾丸蛋白质组学和代谢组学综合分析:砷诱导雄性生殖毒性的机制

DOI:
10.1038/srep32518
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发表时间:
2016-09-02
期刊:
影响因子:
4.6
通讯作者:
Shen H
Shen H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Huang Q;Luo L;Alamdar A;Zhang J;Liu L;Tian M;Eqani SA;Shen H

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砷是一种广泛存在于环境中的类金属,其暴露具有广泛的毒性效应。然而,目前对砷致雄性生殖毒性的认识尚不全面,其机制也不清楚。我们的研究结果表明,砷暴露降低睾酮水平和精子质量的大鼠。本研究旨在通过蛋白质组学和代谢组学相结合的方法,探讨砷暴露对大鼠睾丸蛋白质组和代谢组的整体影响。砷处理显著改变了70种蛋白质(36种上调,34种下调)和13种代谢产物(8种增加,5种减少)的丰度。其中19种蛋白质和2种代谢产物与男性生殖系统发育和功能有关,包括精子发生、精子功能和受精、生育力、内生殖器发育和交配行为。进一步提出,砷主要通过异常调节这些男性生殖相关蛋白和代谢物来损害精子发生和受精,这可能是由ERK/AKT/NF-κ B依赖性信号通路介导的。总体而言,这些研究结果将有助于我们了解砷引起的男性生殖毒性的机制,并从这些研究中发现有用的生物标志物指示砷暴露。
Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.
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