Edlow A G, Hui L, Wick H C, Fried I, Bianchi D W
Mother Infant Research Institute and Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA, USA.
Department of Perinatal Medicine, Mercy Hospital for Women, Heidelberg, Vic., Australia.
BJOG. 2016 Jan;123(2):180-9. doi: 10.1111/1471-0528.13795.
To analyse 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 centre.
Eight obese (body mass index ≥30 kg/m(2)) and eight lean (body mass index <25 kg/m(2)) pregnant women undergoing prelabour caesarean delivery at term.
Women were matched for gestational age and fetal sex. Cord blood RNA was extracted and hybridised 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.
A total of 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 signalling were significantly activated; those related to insulin receptor signalling, 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 signalling, glucose and lipid homeostasis, and oxidative stress. This may have implications for postnatal neurodevelopment and metabolism.
利用脐带血分析足月胎儿的基因表达，以深入了解母亲肥胖对人类发育的影响。
前瞻性病例对照研究。
学术性三级医疗中心。
8名肥胖（体重指数≥30 kg/m²）和8名消瘦（体重指数<25 kg/m²）的足月妊娠妇女，她们均接受了临产前剖宫产。
根据孕周和胎儿性别对妇女进行匹配。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校正来识别差异调节基因。使用Ingenuity Pathway Analysis、BioGPS和带有胎儿特异性注释的基因集富集分析进行功能分析。Z值≥2.0或P值<0.01被认为具有统计学意义。
肥胖妇女胎儿中差异调节基因的功能。
共鉴定出701个差异调节基因，其表达谱表明肥胖妇女胎儿存在神经退行性变、感觉神经元存活率降低和神经发生减少。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。在肥胖妇女胎儿中差异调节的26个组织特异性基因中，有6个定位于胎儿大脑。
母亲肥胖会影响足月胎儿的基因表达，涉及大脑发育失调、炎症和免疫信号、葡萄糖和脂质稳态以及氧化应激。这可能对产后神经发育和代谢产生影响。
