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镉暴露后小鼠睾丸和精子中长链非编码RNA的失调

Dysregulation of long noncoding RNAs in mouse testes and spermatozoa after exposure to cadmium.

作者信息

Gao Fengxin, Zhang Peng, Zhang Hongyan, Zhang Yunhui, Zhang Yunwen, Hao Qingyun, Zhang Xiaoning

机构信息

Institute of Life Science and School of Life Science, Nanchang University, Nanchang 330031, PR China.

Institute of Life Science and School of Life Science, Nanchang University, Nanchang 330031, PR China.

出版信息

Biochem Biophys Res Commun. 2017 Feb 26;484(1):8-14. doi: 10.1016/j.bbrc.2017.01.091. Epub 2017 Jan 19.

Abstract

There is increasing evidence that cadmium (Cd) exposure can cause male subfertility and even complete infertility in mammals. Long noncoding (lnc) RNAs are critical for spermatogenesis, and their dysregulation might lead to male infertility. However, whether they are involved in Cd-induced subfertility is unknown. Here we found that intraperitoneal exposure to Cd in mice led to male subfertility indicated by reductions in testicular sperm production and motility, and by abnormal morphology. Testicular and sperm RNAs were used to investigate lncRNA expression profiles by strand-specific RNA sequencing at the transcriptome level to help determine any RNA-related mechanisms in Cd-induced subfertility. The Cd-treated testes and spermatozoa exhibited aberrant expression profiles for lncRNAs and mRNAs. Of the lncRNAs, there were 139 with upregulated expression and 174 with downregulated expression in testes; in contrast, 685 were upregulated and 375 were downregulated in spermatozoa. For mRNA expression, 214 were upregulated and 226 were downregulated in testes; 272 were upregulated and 111 were downregulated in spermatozoa. Gene ontology and pathway analyses showed that the functions of differentially expressed lncRNA targets and mRNAs were closely linked with many processes involved in spermatogenesis. Additionally, many newly identified lncRNAs showed inducible expression, suggesting that they might be good candidate markers for Cd-induced male reproductive toxicity. This study provides a preliminary database for further exploring lncRNA-related mechnisms in male infertility induced by Cd.

摘要

越来越多的证据表明,镉(Cd)暴露可导致哺乳动物雄性生育力低下,甚至完全不育。长链非编码(lnc)RNA对精子发生至关重要,其失调可能导致男性不育。然而,它们是否参与镉诱导的生育力低下尚不清楚。在此,我们发现,小鼠腹腔注射镉会导致雄性生育力低下,表现为睾丸精子生成和活力降低以及形态异常。利用睾丸和精子RNA,通过链特异性RNA测序在转录组水平上研究lncRNA表达谱,以帮助确定镉诱导的生育力低下中任何与RNA相关的机制。镉处理的睾丸和精子中lncRNA和mRNA呈现异常表达谱。在lncRNA中,睾丸中有139个表达上调,174个表达下调;相比之下,精子中有685个表达上调,375个表达下调。对于mRNA表达,睾丸中有214个上调,226个下调;精子中有272个上调,111个下调。基因本体论和通路分析表明,差异表达的lncRNA靶标和mRNA的功能与精子发生中的许多过程密切相关。此外,许多新鉴定的lncRNA显示出可诱导表达,表明它们可能是镉诱导的雄性生殖毒性的良好候选标志物。本研究为进一步探索镉诱导的男性不育中lncRNA相关机制提供了初步数据库。

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