Daniel Zoe, Swali Angelina, Emes Richard, Langley-Evans Simon C
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, LE12 5RD UK.
School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Loughborough, UK ; Advanced Data Analysis Centre, University of Nottingham, Sutton Bonington, Loughborough, UK.
Genes Nutr. 2016 Oct 12;11:27. doi: 10.1186/s12263-016-0541-3. eCollection 2016.
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.
大鼠孕期胎儿暴露于母体低蛋白饮食与成年后的高血压、肾功能障碍和代谢紊乱有关。当饮食干预仅针对妊娠的前半段时，这些影响就会出现。据推测，妊娠早期蛋白质限制会影响胎盘基因表达，这可能为将母体饮食与后期后果联系起来的机制提供线索。
怀孕大鼠从受孕到妊娠第13天喂食对照饮食或低蛋白饮食。收集胎盘并使用Illumina平台进行RNA测序。
蛋白质限制使胎盘中67个基因下调，24个基因上调。 Ingenuity通路分析显示，与胆固醇和脂蛋白运输及代谢相关的通路有显著富集，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。这些过程的核心基因包括载脂蛋白ApoB、ApoA2和ApoC2、微粒体甘油三酯转移蛋白（Mttp）、网格蛋白内吞受体cubilin、转录因子视黄醇结合蛋白4（Rbp4）和转甲状腺素蛋白（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RNA测序的结果，并表明蛋白质限制的影响通常很显著（cubilin上调32倍，apoC2上调17.6倍）。研究结果表明，特定通路中的基因表达在妊娠第13天的大鼠胎盘中受到母体蛋白质限制的调节。
胆固醇运输的变化可能导致胎儿组织发育改变，从而在以后的生活中引发疾病风险。
