Ogawa Tetsuo, Rakwal Randeep, Shibato Junko, Sawa Chika, Saito Tomomi, Murayama Aya, Kuwagata Makiko, Kageyama Haruaki, Yagi Michiko, Satoh Kazue, Shioda Seiji
Anti-aging Medicine Funded Research Laboratories, Showa University School of Medicine, Tokyo, Japan.
Congenit Anom (Kyoto). 2011 Sep;51(3):110-25. doi: 10.1111/j.1741-4520.2011.00315.x.
Human epidemiological evidence has led scientists to theorize that undernutrition during gestation is an important early origin of adult diseases. Animal models have successfully demonstrated that maternal diet could contribute to some adult diseases. Undernutrition is perceived harmful in pregnant women, whereas calorie restriction is a strategy proven to extend healthy and maximum lifespan in adult. This diagrammatically opposite effect of nutritional condition might provide us with hints to search for genes underlying health conditions. Here, we have initiated a study examining the effect of undernutrition on maternal and fetal livers, utilizing high-throughput DNA microarray analysis for screening genome-wide changes in their transcriptomes. Briefly, pregnant mice were exposed to food deprivation (FD) on gestation day (GD) 17, and cesarean section was performed on GD18. Control mice were supplied with chow ad libitum until sacrifice. Total RNA extracted from mother and fetal livers for each control and treatment (FD) was analyzed with an Agilent mouse whole genome DNA chip. A total of 3058 and 3126 up- (>1.5-fold) and down- (<0.75-fold) regulated genes, and 1475 and 1225 up- (>1.5-fold) and down- (<0.75-fold) regulated genes showed differential expression at the mRNA level, in the maternal and fetal livers, respectively. Interestingly, 103 genes up-regulated in the mother were down-regulated in the fetus, whereas 108 down-regulated maternal genes were up-regulated in the fetus; these 211 genes are potential candidates related to longevity or health. The role of some of these genes, in context of the proposed mechanisms for developmental origins of health and disease is discussed.
人类流行病学证据使科学家们推测,孕期营养不良是成人疾病的一个重要早期根源。动物模型已成功证明,母体饮食可能导致某些成人疾病。营养不良被认为对孕妇有害,而热量限制是一种已被证明可延长成年人健康和最长寿命的策略。这种营养状况在图表上呈现出的相反效果可能会为我们寻找健康状况背后的基因提供线索。在此,我们启动了一项研究,通过高通量DNA微阵列分析来检测营养不良对母体和胎儿肝脏的影响,以筛选其转录组在全基因组范围内的变化。简要来说,在妊娠第17天,将怀孕小鼠暴露于食物剥夺(FD)环境中,并于妊娠第18天进行剖腹产。对照小鼠随意进食直至处死。从每个对照和处理组(FD)的母体和胎儿肝脏中提取的总RNA,使用安捷伦小鼠全基因组DNA芯片进行分析。在母体和胎儿肝脏中,分别有3058个和3126个上调(>1.5倍)和下调(<0.75倍)的基因,以及1475个和1225个上调(>1.5倍)和下调(<0.75倍)的基因在mRNA水平上表现出差异表达。有趣的是,在母体中上调的103个基因在胎儿中下调,而在母体中下调的108个基因在胎儿中上调;这211个基因是与长寿或健康相关的潜在候选基因。本文讨论了其中一些基因在所提出的健康与疾病发育起源机制中的作用。