Maternal Pregnancy Diet Effect on Fetal Brain Transcriptome. Maternal Pregnancy Diet Effect on Fetal Brain Transcriptome

Maternal over- and undernutrition in pregnancy plays a critical role in fetal brain development and function. The effects of different maternal diet compositions on intrauterine programming of the fetal brain in the absence of maternal obesity or maternal undernutrition is a lesser-explored area. The goal of this study was to investigate the impact of two different maternal diets on fetal brain gene expression signatures, fetal/neonatal growth, and neonatal behavior in a mouse model. Female C57Bl/6J mice were fed one of two commercially-available chow diets (pelleted vs. powdered) with differing micronutrient and carbohydrate compositions throughout pregnancy and lactation. The powdered chow diet was richer in carbohydrates and lower in micronutrients than the pelleted chow diet, among other differences. On embryonic day 15.5, embryos were weighed and measured. Fetal brains were snap frozen. RNA was extracted from fetal forebrains for five fetuses per diet group and hybridized to whole genome expression microarrays. Functional analyses identified significant upregulation of canonical pathways and upstream regulators involved in cell cycle regulation, synaptic plasticity, and sensory nervous system development in the fetal brain, and significant downregulation of pathways related to cell and embryo death. Pathways related to DNA damage response, humoral and cell-mediated immune response, carbohydrate and lipid metabolism, small molecule biosynthesis, and amino acid metabolism were also dysregulated. Maternal dietary content is an important variable for researchers evaluating fetal brain development and offspring behavior to consider. Selection of a chow diet matched for micronutrients is crucial to avoid unexpected or undesired effects on offspring brain development and behavior. Overall design: 10 samples, 2 groups of 5 biological replicates

妊娠期母体营养过剩与营养不足，对胎儿大脑发育及功能具有关键影响。在无母体肥胖或营养不足的情况下，不同母体饮食组成对胎儿大脑宫内程序化的影响，仍是一个较少被探索的研究领域。本研究旨在以小鼠为模型，探究两种不同母体饮食对胎儿大脑基因表达特征、胎儿/新生小鼠生长以及新生小鼠行为的影响。
将雌性C57Bl/6J小鼠在妊娠及哺乳期，饲喂两种商品化普通饲料中的一种：颗粒型饲料与粉状饲料，二者的微量营养素与碳水化合物组成存在差异。除其他差异外，粉状饲料相较于颗粒型饲料，碳水化合物含量更高，微量营养素含量更低。
在胚胎发育第15.5天时，对胚胎进行称重与体长测量，并将胎儿大脑快速冷冻保存。从每个饲料组的5个胎儿前脑中提取RNA，将其与全基因组表达微阵列进行杂交。功能分析结果显示，胎儿大脑中涉及细胞周期调控、突触可塑性以及感觉神经系统发育的经典通路与上游调控因子显著上调，而与细胞及胚胎死亡相关的通路则显著下调。与DNA损伤应答、体液及细胞介导免疫应答、碳水化合物与脂质代谢、小分子生物合成以及氨基酸代谢相关的通路同样存在表达失调。
母体饮食组成是评估胎儿大脑发育及子代行为的研究人员需要考量的重要变量。选择微量营养素配比匹配的普通饲料，对避免对子代大脑发育及行为产生非预期不良影响至关重要。
实验整体设计：共10个样本，分为2组，每组包含5个生物学重复。