Maternal obesity affects fetal neurodevelopmental and metabolic gene expression: a pilot study.
Maternal obesity affects fetal neurodevelopmental and metabolic gene expression: a pilot study.
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DOI：
10.1371/journal.pone.0088661
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Bianchi DW
中科院分区：
文献类型：
--
作者：
Edlow AG;Vora NL;Hui L;Wick HC;Cowan JM;Bianchi DW
在美国，三分之一的孕妇是肥胖的。他们的后代患神经发育和代谢疾病的风险增加。基本的分子机制知之甚少。我们进行了一个全面的基因表达分析中期妊娠羊水无细胞胎儿RNA在肥胖和瘦孕妇。这项前瞻性初步研究包括8名肥胖（BMI≥30）和8名瘦（BMI<25）妇女，她们接受了临床指征的中期妊娠遗传穿刺术。受试者的胎龄和胎儿性别相匹配。排除核型异常或结构异常的胎仔。从羊水中提取无细胞胎儿RNA并与全基因组表达阵列杂交。使用具有Benjamini-Hochberg校正的配对t检验（错误发现率<0.05）鉴定在8/8个肥胖-消瘦对中显著差异调节的基因。生物学解释用Influencity Pathway Analysis和BioGPS基因表达图谱进行。在肥胖孕妇的胎儿中，有205个基因被显著差异调节。载脂蛋白D是一种在中枢神经系统中高度表达的基因，是脂质调节的组成部分，是上调最多的基因（9倍）。凋亡性细胞死亡显著下调，特别是在涉及大脑皮层的神经系统通路内。预测肥胖妇女的胎儿中转录调节因子雌激素受体、FOS和STAT 3的激活，提示促雌激素、促炎环境。母亲肥胖早在孕中期就影响胎儿神经发育和代谢基因表达。这些发现可能对肥胖妇女后代的出生后神经发育和代谢异常有影响。
One in three pregnant women in the United States is obese. Their offspring are at increased risk for neurodevelopmental and metabolic morbidity. Underlying molecular mechanisms are poorly understood. We performed a global gene expression analysis of mid-trimester amniotic fluid cell-free fetal RNA in obese versus lean pregnant women. This prospective pilot study included eight obese (BMI≥30) and eight lean (BMI<25) women undergoing clinically indicated mid-trimester genetic amniocentesis. Subjects were matched for gestational age and fetal sex. Fetuses with abnormal karyotype or structural anomalies were excluded. Cell-free fetal RNA was extracted from amniotic fluid and hybridized to whole genome expression arrays. Genes significantly differentially regulated in 8/8 obese-lean pairs were identified using paired t-tests with the Benjamini-Hochberg correction (false discovery rate of <0.05). Biological interpretation was performed with Ingenuity Pathway Analysis and the BioGPS gene expression atlas. In fetuses of obese pregnant women, 205 genes were significantly differentially regulated. Apolipoprotein D, a gene highly expressed in the central nervous system and integral to lipid regulation, was the most up-regulated gene (9-fold). Apoptotic cell death was significantly down-regulated, particularly within nervous system pathways involving the cerebral cortex. Activation of the transcriptional regulators estrogen receptor, FOS, and STAT3 was predicted in fetuses of obese women, suggesting a pro-estrogenic, pro-inflammatory milieu. Maternal obesity affects fetal neurodevelopmental and metabolic gene expression as early as the second trimester. These findings may have implications for postnatal neurodevelopmental and metabolic abnormalities described in the offspring of obese women.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
8
作者：
Boney, CM;Verma, A;Vohr, BR
通讯作者：
Vohr, BR
DOI：
10.1016/j.bbadis.2009.08.007
发表时间：
2009-11
影响因子：
6.2
作者：
Clementi, Alicia H.;Gaudy, Allison M.;van Rooijen, Nico;Pierce, Robert H.;Mooney, Robert A.
通讯作者：
Mooney, Robert A.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4.4
作者：
Greenhill, Claire J.;Rose-John, Stefan;Jenkins, Brendan J.
通讯作者：
Jenkins, Brendan J.