Maternal and Fetal Health Research Centre, Division of Developmental Biology & Medicine, School of Medical Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK.
Maternal and Fetal Health Research Centre, Central Manchester University Hospitals NHS Foundation Trust, St Mary's Hospital, Manchester Academic Health sciences Centre, Manchester, M13 9WL, UK.
Sci Rep. 2018 Mar 27;8(1):5270. doi: 10.1038/s41598-018-22535-y.
The specific consequences of hyperglycaemia on placental metabolism and function are incompletely understood but likely contribute to poor pregnancy outcomes associated with diabetes mellitus (DM). This study aimed to identify the functional biochemical pathways perturbed by placental exposure to high glucose levels through integrative analysis of the trophoblast transcriptome and metabolome. The human trophoblast cell line, BeWo, was cultured in 5 or 25 mM glucose, as a model of the placenta in DM. Transcriptomic analysis using microarrays, demonstrated 5632 differentially expressed gene transcripts (≥± 1.3 fold change (FC)) following exposure to high glucose. These genes were used to generate interactome models of transcript response using BioGRID (non-inferred network: 2500 nodes (genes) and 10541 protein-protein interactions). Ultra performance-liquid chromatography-mass spectrometry (MS) and gas chromatography-MS analysis of intracellular extracts and culture medium were used to assess the response of metabolite profiles to high glucose concentration. The interactions of altered genes and metabolites were assessed using the MetScape interactome database, resulting in an integrated model of systemic transcriptome (2969 genes) and metabolome (41 metabolites) response within placental cells exposed to high glucose. The functional pathways which demonstrated significant change in response to high glucose included fatty acid β-oxidation, phospholipid metabolism and phosphatidylinositol phosphate signalling.
高血糖对胎盘代谢和功能的具体影响尚不完全清楚，但可能与糖尿病（DM）相关的不良妊娠结局有关。本研究旨在通过对滋养层转录组和代谢组进行综合分析，确定胎盘暴露于高葡萄糖水平下受干扰的功能生化途径。BeWo 人滋养层细胞系在 5 或 25mmol/L 葡萄糖中培养，作为 DM 中胎盘的模型。使用微阵列进行转录组分析，显示高葡萄糖暴露后有 5632 个差异表达基因转录本（≥±1.3 倍变化（FC））。这些基因用于使用 BioGRID 生成转录响应的互作网络模型（非推断网络：2500 个节点（基因）和 10541 个蛋白质-蛋白质相互作用）。使用超高效液相色谱-质谱（MS）和气相色谱-MS 分析细胞内提取物和培养基，以评估代谢谱对高葡萄糖浓度的反应。使用 MetScape 互作网络数据库评估改变的基因和代谢物的相互作用，得到胎盘细胞暴露于高葡萄糖时系统转录组（2969 个基因）和代谢组（41 种代谢物）反应的综合模型。对高葡萄糖反应显示显著变化的功能途径包括脂肪酸β-氧化、磷脂代谢和磷脂酰肌醇磷酸信号转导。
