Radford B N, Han V K M
Department of Biochemistry, Schulich School of Medicine & Dentistry, Western University,London, ON,Canada.
J Dev Orig Health Dis. 2019 Aug;10(4):469-478. doi: 10.1017/S2040174418000983. Epub 2018 Dec 3.
Fetal growth restriction (FGR) is a pregnancy condition in which fetal growth is suboptimal for gestation, and this population is at increased risk for type 2 diabetes as adults. In humans, maternal malnutrition and placental insufficiency are the most common causes of FGR, and both result in fetal undernutrition. We hypothesized that maternal nutrient restriction (MNR) in mice will cause FGR and alter glucose metabolism in adult offspring. Pregnant CD-1 mice were subjected to MNR (70% of average ad libitum) or control (ad libitum) from E6.5 to birth. Following birth, mice were fostered by mothers on ad libitum feeds. Weight, blood glucose, glucose tolerance and tissue-specific insulin sensitivity were assessed in male offspring. MNR resulted in reduced fetal sizes but caught up to controls by 3 days postnatal age. As adults, glucose intolerance was detected in 19% of male MNR offspring. At 6 months, liver size was reduced (P = 0.01), but pAkt-to-Akt ratios in response to insulin were increased 2.5-fold relative to controls (P = 0.004). These data suggest that MNR causes FGR and long-term glucose intolerance in a population of male offspring similar to human populations. This mouse model can be used to investigate the impacts of FGR on tissues of importance in glucose metabolism.
胎儿生长受限（FGR）是一种妊娠状况，即胎儿生长未达妊娠期的最佳状态，且该群体成年后患2型糖尿病的风险增加。在人类中，母体营养不良和胎盘功能不全是FGR最常见的原因，两者都会导致胎儿营养不足。我们假设，小鼠母体营养限制（MNR）会导致FGR，并改变成年后代的葡萄糖代谢。从胚胎第6.5天至出生，对怀孕的CD-1小鼠进行MNR（自由摄食量的70%）或对照（自由摄食）处理。出生后，小鼠由自由摄食的母亲抚养。对雄性后代评估体重、血糖、葡萄糖耐量和组织特异性胰岛素敏感性。MNR导致胎儿体型减小，但在出生后3天赶上对照组。成年后，19%的雄性MNR后代检测到葡萄糖不耐受。6个月时，肝脏大小减小（P = 0.01），但相对于对照组，胰岛素刺激后的pAkt与Akt比率增加了2.5倍（P = 0.004）。这些数据表明，MNR会导致雄性后代群体出现FGR和长期葡萄糖不耐受，类似于人类群体。该小鼠模型可用于研究FGR对葡萄糖代谢重要组织的影响。
