Regulation of fetal liver transcription by maternal nutritional stress

Pregnancy is a time of extreme metabolic demand that requires coordinated adaptations between mother and fetus. To determine the contributions of maternal and fetal metabolism to metabolic plasticity during gestation, mice with a liver-specific Carnitine Palmitoyltransferase-2 knockout mice (Cpt2-/-), or Pparα KO mice were subjected to late-gestation nutrient stress, a 24hr fast from E16.5 to E17.5. The fetal response to maternal fasting was dominated by maternal lipid metabolism as the loss of maternal hepatic fatty acid oxidation or Ppar-alpha signaling accelerated fetal liver transcriptional programing. These data show that maternal nutritional environment is a major driver of perinatal metabolic programing and plasticity. Examination of wild-type and Ppara KO E17.5 fetal liver following a 24hr fast in WT, Cpt2-/-, and Ppara KO dams, with 4 biological replicates each.妊娠是一段代谢需求极高的时期，此过程需要母体与胎儿之间开展协同适应性调控。为明确妊娠期间母体与胎儿代谢对代谢可塑性的贡献，本研究对携带肝脏特异性肉碱棕榈酰转移酶2（Carnitine Palmitoyltransferase-2, Cpt2）敲除的小鼠（Cpt2-/-），或过氧化物酶体增殖物激活受体α（Peroxisome Proliferator-Activated Receptor Alpha, Pparα）敲除（Pparα KO）的孕鼠，施加妊娠晚期营养应激：即从胚胎期16.5天（E16.5）至胚胎期17.5天（E17.5）进行24小时禁食。母体禁食引发的胎儿响应以母体脂质代谢调控为主，当母体肝脏脂肪酸氧化途径缺失或Pparα信号通路受到抑制时，会加速胎儿肝脏的转录编程过程。上述研究数据表明，母体营养环境是围产期代谢编程与代谢可塑性的关键驱动因素。本研究对野生型（Wild Type, WT）、Cpt2-/-及Pparα KO孕鼠实施24小时禁食后，采集其胚胎期17.5天的胎儿肝脏样本进行检测，每组设置4次生物学重复。