Department of Obstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada.
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
Pediatr Res. 2017 Jul;82(1):141-147. doi: 10.1038/pr.2017.92. Epub 2017 May 24.
BackgroundWe determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts markers for tissue hypoxia, implicating a mechanistic role for chronic hypoxia.MethodsGuinea pigs were fed ad libitum (Control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1), a marker of tissue hypoxia, was injected into pregnant sows. Fetuses were then necropsied and liver, kidney, and placental tissues were processed for erythropoietin (EPO), EPO-receptor (EPOR), and vascular endothelial growth factor (VEGF) protein levels, and for HP-1 immunoreactivity (IR).ResultsFGR-MNR fetuses were 36% smaller with asymmetrical growth restriction compared to controls. EPO and VEGF protein levels were increased in the female FGR-MNR fetuses, providing support for hypoxic stimulus and linkage to increased erythropoiesis, but not in the male FGR-MNR fetuses, possibly reflecting a weaker link between oxygenation and erythropoiesis. HP-1 IR was increased in the liver and kidneys of both male and female FGR-MNR fetuses as an index of local tissue hypoxia, but with no changes in the placenta.ConclusionChronic hypoxia is likely to be an important signaling mechanism for the decreased fetal growth seen with maternal undernutrition and appears to be post-placental in nature.
我们研究了豚鼠的母体营养限制（MNR）是否导致胎儿生长受限（FGR），并影响了组织缺氧的标志物，这暗示了慢性缺氧的一种机制作用。
在怀孕前，豚鼠自由进食（对照组）或摄入 70%的对照饮食，然后在妊娠中期切换到 90%（MNR 组）。接近分娩时，向怀孕的母猪注射缺氧探针-1（HP-1），这是一种组织缺氧的标志物。然后对胎儿进行尸检，并处理肝、肾和胎盘组织，以检测红细胞生成素（EPO）、EPO 受体（EPOR）和血管内皮生长因子（VEGF）的蛋白水平，以及 HP-1 免疫反应性（IR）。
FGR-MNR 胎儿比对照组小 36%，且生长受限呈不对称性。雌性 FGR-MNR 胎儿的 EPO 和 VEGF 蛋白水平升高，为缺氧刺激提供了支持，并与增加的红细胞生成相关联，但雄性 FGR-MNR 胎儿则没有，这可能反映了氧气供应与红细胞生成之间的联系较弱。HP-1 IR 在雄性和雌性 FGR-MNR 胎儿的肝脏和肾脏中均增加，作为局部组织缺氧的指标，但胎盘没有变化。
慢性缺氧可能是母体营养不良导致胎儿生长受限的一个重要信号机制，而且似乎是胎盘后的性质。
