The effect of maternal undernutrition on the rat placental transcriptome: protein restriction up-regulates cholesterol transport.
The effect of maternal undernutrition on the rat placental transcriptome: protein restriction up-regulates cholesterol transport.
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DOI：
10.1186/s12263-016-0541-3
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发表时间：
2016
影响因子：
3.5
通讯作者：
Langley-Evans SC
中科院分区：
文献类型：
--
作者：
Daniel Z;Swali A;Emes R;Langley-Evans SC
大鼠妊娠期母体低蛋白饮食对胎儿的影响与成年期高血压、肾功能不全和代谢紊乱有关。当饮食控制仅针对怀孕的前半期时，这些影响就存在了。据推测，妊娠早期蛋白质限制会影响胎盘基因表达，这可能会提供线索的机制，母亲的饮食，后来的后果。妊娠大鼠从受孕到妊娠第13天喂食对照或低蛋白饮食。收集胎盘并使用Illumina平台进行RNA测序。蛋白质限制性内切酶在胎盘中下调了67个基因，上调了24个基因。免疫途径分析显示，与胆固醇和脂蛋白转运和代谢相关的途径显著富集，包括动脉粥样硬化信号传导、网格蛋白介导的内吞作用、LXR/RXR和FXR/RXR激活。这些过程的中心基因包括载脂蛋白ApoB、ApoA 2和ApoC 2、微粒体甘油三酯转移蛋白（Mttp）、网格蛋白-内吞作用受体cubilin、转录因子视黄醇结合蛋白4（Rbp 4）和转丝素蛋白（Ttr;一种视黄醇和甲状腺激素转运蛋白）。实时PCR测量在很大程度上证实了RNASeq的发现，并表明蛋白质限制的影响通常是惊人的（cubilin上调32倍，apoC 2上调17.6倍）。研究结果表明，在特定途径的基因表达调制的母体蛋白质限制在第13天的大鼠胎盘。胆固醇转运的变化可能会改变胎儿的组织发育，从而增加日后患病的风险。本文的在线版本（doi：10.1186/s12263-016-0541-3）包含补充材料，可供授权用户使用。
Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences. Pregnant rats were fed control or a low protein diet from conception to day 13 gestation. Placentas were collected and RNA sequencing performed using the Illumina platform. Protein restriction down-regulated 67 genes and up-regulated 24 genes in the placenta. Ingenuity pathway analysis showed significant enrichment in pathways related to cholesterol and lipoprotein transport and metabolism, including atherosclerosis signalling, clathrin-mediated endocytosis, LXR/RXR and FXR/RXR activation. Genes at the centre of these processes included the apolipoproteins ApoB, ApoA2 and ApoC2, microsomal triglyceride transfer protein (Mttp), the clathrin-endocytosis receptor cubilin, the transcription factor retinol binding protein 4 (Rbp4) and transerythrin (Ttr; a retinol and thyroid hormone transporter). Real-time PCR measurements largely confirmed the findings of RNASeq and indicated that the impact of protein restriction was often striking (cubilin up-regulated 32-fold, apoC2 up-regulated 17.6-fold). The findings show that gene expression in specific pathways is modulated by maternal protein restriction in the day-13 rat placenta. Changes in cholesterol transport may contribute to altered tissue development in the fetus and hence programme risk of disease in later life. The online version of this article (doi:10.1186/s12263-016-0541-3) contains supplementary material, which is available to authorized users.