Assessing the fetal effects of maternal obesity via transcriptomic analysis of cord blood: a prospective case-control study.
Assessing the fetal effects of maternal obesity via transcriptomic analysis of cord blood: a prospective case-control study.
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DOI：
10.1111/1471-0528.13795
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Bianchi DW
中科院分区：
文献类型：
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作者：
Edlow AG;Hui L;Wick HC;Fried I;Bianchi DW
目的：利用脐带血分析足月胎儿基因表达，为了解母体肥胖对人类发育的影响提供依据。前瞻性病例对照研究。学术三级护理中心。8名肥胖（BMI ≥ 30）和8名消瘦（BMI < 25）孕妇在足月时接受产前剖宫产。妇女的胎龄和胎儿性别相匹配。提取脐带血RNA并与基因表达阵列杂交。使用配对t检验和Benjamini-Hochberg校正鉴定差异调节基因。功能分析使用Influence Pathway Analysis、BioGPS和具有胎儿特异性注释的基因集富集分析进行。认为Z评分≥ 2.0或p值< 0.01具有显著性。差异调控基因在肥胖妇女胎儿中的功能。701差异调节基因被确定，产生一个表达谱牵连神经变性，感觉神经元的存活率下降，并减少在胎儿的肥胖妇女的神经发生。与炎症信号相关的上游调节因子被显著激活;与胰岛素受体信号、脂质稳态、轴突导向调节和细胞对氧化应激反应相关的上游调节因子被显著抑制。在26个在肥胖妇女胎儿中差异调节的组织特异性基因中，有6个定位于胎儿大脑。母体肥胖影响足月胎儿基因表达，涉及脑发育失调、炎症和免疫信号传导、葡萄糖和脂质稳态以及氧化应激。这可能对出生后的神经发育和代谢有影响。
To analyze fetal gene expression at term using umbilical cord blood, in order to provide insights into the effects of maternal obesity on human development. Prospective case-control study. Academic tertiary care center. Eight obese (BMI ≥ 30) and eight lean (BMI < 25) pregnant women undergoing pre-labor cesarean delivery at term. Women were matched for gestational age and fetal sex. Cord blood RNA was extracted and hybridized to gene expression arrays. Differentially regulated genes were identified using paired t-tests and the Benjamini-Hochberg correction. Functional analyses were performed using Ingenuity Pathway Analysis, BioGPS, and Gene Set Enrichment Analysis with a fetal-specific annotation. Z-scores ≥ 2.0 or p-values < 0.01 were considered significant. Functions of differentially regulated genes in fetuses of obese women. 701 differentially regulated genes were identified, producing an expression profile implicating neurodegeneration, decreased survival of sensory neurons, and decreased neurogenesis in the fetuses of obese women. Upstream regulators related to inflammatory signaling were significantly activated; those related to insulin receptor signaling, lipid homeostasis, regulation of axonal guidance, and cellular response to oxidative stress were significantly inhibited. Of 26 tissue-specific genes that were differentially regulated in fetuses of obese women, six mapped to the fetal brain. Maternal obesity affects fetal gene expression at term, implicating dysregulated brain development, inflammatory and immune signaling, glucose and lipid homeostasis, and oxidative stress. This may have implications for postnatal neurodevelopment and metabolism.