RNA-Seq identifies key reproductive gene expression alterations in response to cadmium exposure.

RNA-Seq identifies key reproductive gene expression alterations in response to cadmium exposure.
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RNA-Seq 识别镉暴露引起的关键生殖基因表达变化

DOI:
10.1155/2014/529271
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发表时间:
2014
影响因子:
--
通讯作者:
Zhong S
Zhong S
中科院分区:
生物学3区
文献类型:
--
作者:
Hu H;Lu X;Cen X;Chen X;Li F;Zhong S

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镉是一种常见的有毒物质,对许多组织有害。尽管镉处理后不同组织中出现了大量转录特征,但镉引起雄性生殖毒性的相关基因及其分子机制尚不清楚。在这里,我们观察到,在啮齿类动物饲料中给予不同量的镉的小鼠六个月后,其血清睾酮水平降低。然后,我们进行RNA-seq全面研究小鼠睾丸转录组,以进一步阐明其机制。我们的结果表明,数百个基因的表达在镉处理后发生了显着变化。特别是,我们发现了几个转录签名密切相关的激素,配子生成和有性生殖的生物过程的调节,分别。结果表明,镉暴露抑制了睾酮合成关键酶基因星星、Cyp 11 a1和Cyp 17 a1的表达。为了更好地理解镉介导的基因转录调控机制,我们计算分析了差异表达基因的转录因子结合位点和microRNA靶点。我们的研究结果表明,镉暴露的生殖毒性是牵连在几个生物过程和转录调控的多层失调在小鼠。
Cadmium is a common toxicant that is detrimental to many tissues. Although a number of transcriptional signatures have been revealed in different tissues after cadmium treatment, the genes involved in the cadmium caused male reproductive toxicity, and the underlying molecular mechanism remains unclear. Here we observed that the mice treated with different amount of cadmium in their rodent chow for six months exhibited reduced serum testosterone. We then performed RNA-seq to comprehensively investigate the mice testicular transcriptome to further elucidate the mechanism. Our results showed that hundreds of genes expression altered significantly in response to cadmium treatment. In particular, we found several transcriptional signatures closely related to the biological processes of regulation of hormone, gamete generation, and sexual reproduction, respectively. The expression of several testosterone synthetic key enzyme genes, such as Star, Cyp11a1, and Cyp17a1, were inhibited by the cadmium exposure. For better understanding of the cadmium-mediated transcriptional regulatory mechanism of the genes, we computationally analyzed the transcription factors binding sites and the mircoRNAs targets of the differentially expressed genes. Our findings suggest that the reproductive toxicity by cadmium exposure is implicated in multiple layers of deregulation of several biological processes and transcriptional regulation in mice.
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