Winterhager Elke, Gellhaus Alexandra
Electron Microscopy Unit, Imaging Center Essen, University Hospital, University of Duisburg-Essen, Essen, Germany.
Department of Gynecology and Obstetrics, University Hospital, University of Duisburg-Essen, Essen, Germany.
Front Physiol. 2017 Nov 27;8:951. doi: 10.3389/fphys.2017.00951. eCollection 2017.
Although the causes of intrauterine growth restriction (IUGR) have been intensively investigated, important information is still lacking about the role of the placenta as a link from adverse maternal environment to adverse pregnancy outcomes of IUGR and preterm birth. IUGR is associated with an increased risk of cardiovascular, metabolic, and neurological diseases later in life. Determination of the most important pathways that regulate transplacental transport systems is necessary for identifying marker genes as diagnostic tools and for developing drugs that target the molecular pathways. Besides oxygen, the main nutrients required for appropriate fetal development and growth are glucose, amino acids, and fatty acids. Dysfunction in transplacental transport is caused by impairments in both placental morphology and blood flow, as well as by factors such as alterations in the expression of insulin-like growth factors and changes in the mTOR signaling pathway leading to a change in nutrient transport. Animal models are important tools for systematically studying such complex events. Debate centers on whether the rodent placenta is an appropriate tool for investigating the alterations in the human placenta that result in IUGR. This review provides an overview of the alterations in expression and activity of nutrient transporters and alterations in signaling associated with IUGR and compares these findings in rodents and humans. In general, the data obtained by studies of the various types of rodent and human nutrient transporters are similar. However, direct comparison is complicated by the fact that the results of such studies are controversial even within the same species, making the interpretation of the results challenging. This difficulty could be due to the absence of guidelines of the experimental design and, especially in humans, the use of trophoblast cell culture studies instead of clinical trials. Nonetheless, developing new therapy concepts for IUGR will require the use of animal models for gathering robust data about mechanisms leading to IUGR and for testing the effectiveness and safety of the intervention among pregnant women.
尽管对宫内生长受限（IUGR）的病因已进行了深入研究，但关于胎盘作为母体不良环境与IUGR及早产不良妊娠结局之间联系的作用，仍缺乏重要信息。IUGR与日后发生心血管、代谢和神经疾病的风险增加相关。确定调节胎盘转运系统的最重要途径，对于识别作为诊断工具的标记基因以及开发针对分子途径的药物是必要的。除了氧气，胎儿正常发育和生长所需的主要营养物质是葡萄糖、氨基酸和脂肪酸。胎盘转运功能障碍是由胎盘形态和血流受损以及胰岛素样生长因子表达改变和mTOR信号通路变化等因素导致营养物质转运改变引起的。动物模型是系统研究此类复杂事件的重要工具。争论的焦点在于啮齿动物胎盘是否是研究导致人类IUGR的胎盘改变的合适工具。本综述概述了与IUGR相关的营养转运蛋白表达和活性的改变以及信号传导的改变，并比较了啮齿动物和人类的这些发现。一般来说，对各种类型的啮齿动物和人类营养转运蛋白的研究获得的数据是相似的。然而，由于即使在同一物种内此类研究结果也存在争议，使得结果的解释具有挑战性，直接比较变得复杂。这种困难可能是由于缺乏实验设计指南，尤其是在人类研究中，使用滋养层细胞培养研究而非临床试验。尽管如此，开发针对IUGR的新治疗概念将需要使用动物模型来收集关于导致IUGR的机制的可靠数据，并测试干预措施在孕妇中的有效性和安全性。
