Changes in the Metabolic Footprint of Placental Explant-Conditioned Culture Medium Identifies Metabolic Disturbances Related to Hypoxia and Pre-Eclampsia
Changes in the Metabolic Footprint of Placental Explant-Conditioned Culture Medium Identifies Metabolic Disturbances Related to Hypoxia and Pre-Eclampsia
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DOI：
10.1016/j.placenta.2009.08.008
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发表时间：
2009-11-01
期刊：
影响因子：
3.8
通讯作者：
Heazell, A. E. P.
中科院分区：
文献类型：
--
作者：
Dunn, W. B.;Brown, M.;Heazell, A. E. P.
子痫前期（PE）是一种多系统疾病，被认为是由胎盘绒毛滋养细胞受损释放的循环因子介导的。有大量证据表明PE的绒毛组织发生了变化，其中一些变化可以通过在缺氧条件下培养绒毛组织来复制。代谢足迹提供了一种假设生成策略来研究从体外组织释放的因子。本研究探讨了未并发症妊娠（n = 6）和PE妊娠（n = 6）中绒毛滋养细胞释放因子的差异。在这两种情况下，移植的胎盘绒毛片段在1% O-2（缺氧）或6% O-2（胎盘缺氧）中培养96 h。使用超高效液相色谱-质谱（UPLC-MS）分析从血清培养基中消耗和释放的代谢物。在正常妊娠和低氧条件下培养的培养基中，观察到154种代谢足迹特征的相对浓度发生了变化（p < 0.00005）。在低氧和常氧条件下培养的PE与无并发症妊娠的培养基中，21和80的特征也不同（p < 0.00005）。在比较这4组时，在常氧条件下培养的pe衍生培养基中，47种代谢特征的相对浓度与在缺氧条件下培养的正常绒毛组织的条件培养基相似。这些数据提示缺氧可能在PE的胎盘发病机制中起作用。代谢的三个领域被强调为系统生物学研究：谷氨酸和谷氨酰胺，色氨酸代谢和白三烯或前列腺素代谢。2009爱思唯尔有限公司版权所有。
Pre-eclampsia (PE) is a multi-system disorder thought to be mediated by circulating factors released from damaged placental villous trophoblast. There is extensive evidence of changes in the villous tissue in PE, some of which may be replicated by culturing villous tissue in hypoxic conditions. Metabolic footprinting offers a hypothesis-generating strategy to investigate factors released from this tissue in vitro. This study investigated differences in the factors released from villous trophoblast from uncomplicated pregnancies (n = 6) and those with PE (n = 6). In both cases, explanted placental villous fragments were cultured for 96 h in 1% O-2 (hypoxia) or 6% O-2 (placental normoxia). Metabolites consumed from and released into serum-conditioned culture medium were analysed by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS). The relative concentration of 154 features of the metabolic footprint were observed to change in culture medium from uncomplicated pregnancies cultured in normoxic and hypoxic conditions (p < 0.00005). 21 and 80 features were also different in culture medium from PE versus uncomplicated pregnancies cultured in hypoxic and normoxic conditions, respectively (p < 0.00005). When comparing all 4 groups, 47 metabolic features showed a similar relative concentration in PE-derived media cultured in normoxic conditions to conditioned media from normal villous tissue cultured in hypoxic conditions. These data suggest that hypoxia may have a role in the placental pathogenesis of PE. Three areas of metabolism were highlighted for systems biology investigation: glutamate and glutamine, tryptophan metabolism and leukotriene or prostaglandin metabolism. (C) 2009 Elsevier Ltd. All rights reserved.