Hepatic gene expression in male fetuses from maternal nutrient restriction in mice

The aim of this study was to identify fetal adaptations to gene expression in our mouse model of intrauterine growth restriction (IUGR). Starting at E6.5, pregnant CD-1 mice received either control (ad libitum) or 70% of ad libitum food (maternal nutrient restriction [MNR]). At E18.5, fetal right liver lobes were collected from 2 pups/litter in litters with 11-15 pups. Frozen liver was homogenized for RNA isolations. Isolated RNA was sequenced on a HiSeq2500 with an average read depth of 23M reads and a range of 17-31M reads per sample. Reads were aligned to the mm9 transcriptome with Bowtie2. Normalization and differential expression was done with DESeq2, ALDex2 and EdgeR, and genes were considered in the study if they were consistent in 2 or more tools (FDR <0.1). 10 control and 10 MNR samples were analyzed with (2 pups/ litter)

本研究旨在明确宫内生长受限（intrauterine growth restriction, IUGR）小鼠模型中胎鼠的基因表达适应性调控特征。实验自胚胎第6.5天（E6.5）起，将孕CD-1品系小鼠分为两组：对照组给予自由采食，母体营养限制（maternal nutrient restriction, MNR）组的采食剂量为自由采食量的70%。于胚胎第18.5天（E18.5）采集样本，从每窝产仔数为11~15只的孕鼠中，每窝选取2只胎鼠，收集其右肝叶组织。将冻存的肝组织匀浆后进行RNA提取，提取的RNA在HiSeq2500测序平台上完成转录组测序，单样本平均测序深度为23M条读段，单样本读段数分布范围为17~31M条。使用Bowtie2将测序读段比对至mm9转录组；采用DESeq2、ALDex2及EdgeR三种工具进行数据标准化与差异表达分析，将在至少2种工具中结果一致且错误发现率（False Discovery Rate, FDR）小于0.1的基因纳入本研究。最终共分析10个对照组样本与10个MNR组样本，每个样本均来自每窝2只胎鼠的组织。