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妊娠 binge 酒精引起的母体子宫动脉转录组改变。

Gestational binge alcohol-induced alterations in maternal uterine artery transcriptome.

机构信息

Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.

Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, and the Texas A&M Institute of Genome Sciences, TX, USA.

出版信息

Reprod Toxicol. 2019 Aug;87:42-49. doi: 10.1016/j.reprotox.2019.05.053. Epub 2019 May 9.

DOI:10.1016/j.reprotox.2019.05.053
PMID:31078653
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6628922/
Abstract

Binge alcohol exposure during pregnancy results in diminished vessel function and altered proteome in the maternal uterine artery. We aimed to utilize high throughput RNA-seq deep-sequencing to characterize specific effects of binge alcohol exposure during pregnancy on the uterine artery transcriptome, and gain insight into mechanisms underlying alcohol-mediated uterine artery dysfunction. Pregnant Sprague-Dawley rats assigned to Pair-Fed Control or Alcohol groups, received a once-daily orogastric gavage in a binge paradigm. RNA-sequencing using Illumina NextSeq 500, identified 13,941 genes; 40 significantly altered genes were altered by log(fold change) > 2; 27 genes were upregulated and 13 were downregulated in the Alcohol group. Transcripts altered included those which encode for aldehyde dehydrogenases, matrix metalloproteases, and molecules vital for vasodilation and vascular remodeling. Biological pathways that were disproportionally altered by alcohol were proline and citrulline biosynthesis/metabolism. Disruption of these pathways suggests candidate mechanism(s) for alcohol-mediated impairments to the proteome and vascular function.

摘要

孕期 binge 饮酒会导致母体子宫动脉的血管功能下降和蛋白质组改变。我们旨在利用高通量 RNA-seq 深度测序来描述孕期 binge 饮酒对子宫动脉转录组的特定影响,并深入了解酒精介导的子宫动脉功能障碍的机制。将怀孕的 Sprague-Dawley 大鼠分配到配对喂养对照组或酒精组,每天接受一次经口灌胃的 binge 范式。使用 Illumina NextSeq 500 进行 RNA-seq 测序,鉴定出 13941 个基因;酒精组中有 40 个基因的表达发生了显著改变,其对数(fold change)>2;27 个基因上调,13 个基因下调。改变的转录本包括编码醛脱氢酶、基质金属蛋白酶和对血管舒张和血管重塑至关重要的分子的基因。受酒精不成比例改变的生物学途径是脯氨酸和瓜氨酸的生物合成/代谢。这些途径的破坏表明了酒精介导的对蛋白质组和血管功能损伤的候选机制。

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Mechanisms Underlying Chronic Binge Alcohol Exposure-Induced Uterine Artery Dysfunction in Pregnant Rat.慢性 binge 酒精暴露致孕鼠子宫动脉功能障碍的机制。
Alcohol Clin Exp Res. 2018 Apr;42(4):682-690. doi: 10.1111/acer.13602. Epub 2018 Feb 16.
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Chronic binge alcohol consumption during pregnancy alters rat maternal uterine artery pressure response.孕期长期大量饮酒会改变大鼠母体子宫动脉的压力反应。
Alcohol. 2016 Nov;56:59-64. doi: 10.1016/j.alcohol.2016.10.005. Epub 2016 Oct 13.
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