Intrauterine multi-metal exposure is associated with reduced fetal growth through modulation of the placental gene network.
Intrauterine multi-metal exposure is associated with reduced fetal growth through modulation of the placental gene network.
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DOI：
10.1016/j.envint.2018.08.010
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发表时间：
2018-11
影响因子：
11.8
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Deyssenroth MA;Gennings C;Liu SH;Peng S;Hao K;Lambertini L;Jackson BP;Karagas MR;Marsit CJ;Chen J
宫内金属暴露和胎盘突起的异常是导致小于胎龄儿(SGA)的已知因素。然而，到目前为止，研究主要集中在独立影响上，没有考虑到这些标记之间潜在的相互依赖。我们评估了与SGA状态相关的多金属指数和胎盘基因网络模块之间的相互关系，以强调子宫内多金属暴露影响胎儿生长的潜在分子途径。使用从罗德岛儿童健康研究(RICHS，n=195)收集的一组产后母亲脚趾指甲中测量的16种微量金属进行加权分位数和(WQS)回归，并使用贝叶斯核机器回归(BKMR)对得出的SGA相关多金属指数进行确认。我们利用现有的胎盘加权基因共表达网络数据来检验SGA多金属指数和胎盘基因表达之间的相关性。在一个独立的出生队列，新汉普郡出生队列研究(NHBCS，n=237)中，使用RT-PCR来评估精选基因的表达。我们确定了以砷(As)和镉(Cd)为主的多金属指数，该指数与SGA状态呈正相关(优势比=2.73[1.04，7.18])。该指数还与参与“基因表达”(β=−0.02[−0.04，−0.01])和“代谢激素分泌”(β=0.02[0.00，0.05])的胎盘基因模块的表达有关。我们验证了镉暴露与NHBCS中“代谢激素分泌”模块中GRHL1和INHBA基因表达的相关性。我们提出了一种新的方法，整合了先进的生物信息学和生物统计学方法的应用，以描绘潜在的胎盘途径，通过这些途径，微量金属暴露影响胎儿生长。
Intrauterine metal exposures and aberrations in placental processes are known contributors to being born small for gestational age (SGA). However, studies to date have largely focused on independent effects, failing to account for potential interdependence among these markers. We evaluated the inter-relationship between multi-metal indices and placental gene network modules related to SGA status to highlight potential molecular pathways through which in utero multi-metal exposure impacts fetal growth. Weighted quantile sum (WQS) regression was performed using a panel of 16 trace metals measured in post-partum maternal toe nails collected from the Rhode Island Child Health Study (RICHS, n=195), and confirmation of the derived SGA-related multi-metal index was conducted using Bayesian kernel machine regression (BKMR). We leveraged existing placental weighted gene coexpression network data to examine associations between the SGA multi-metal index and placental gene expression. Expression of select genes were assessed using RT-PCR in an independent birth cohort, the New Hampshire Birth Cohort Study (NHBCS, n=237). We identified a multi-metal index, predominated by arsenic (As) and cadmium (Cd), that was positively associated with SGA status (Odds ratio = 2.73 [1.04, 7.18]). This index was also associated with the expression of placental gene modules involved in “gene expression” (β=−0.02 [−0.04,−0.01]) and “metabolic hormone secretion” (β=0.02 [0.00,0.05]). We validated the association between cadmium exposure and the expression of GRHL1 and INHBA, genes in the “metabolic hormone secretion” module, in NHBCS. We present a novel approach that integrates the application of advanced bioinformatics and biostatistics methods to delineate potential placental pathways through which trace metal exposures impact fetal growth.
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影响因子：
2.7
作者：
Garrett SH;Clarke K;Sens DA;Deng Y;Somji S;Zhang KK
通讯作者：
Zhang KK
影响因子：
3.6
作者：
Green, Benjamin B.;Armstrong, David A.;Marsit, Carmen J.
通讯作者：
Marsit, Carmen J.
关于出生结果和脂肪因子表达的母体和脐带血液中双酚A浓度的生物监测：台湾的一项出生队列研究。
DOI：
10.1186/1476-069x-10-94
发表时间：
2011-11-03
期刊：
Environmental health : a global access science source
影响因子：
--
作者：
Chou WC;Chen JL;Lin CF;Chen YC;Shih FC;Chuang CY
通讯作者：
Chuang CY
评估对化学混合物和癌症风险建模的加权分位数总和回归的评估。
影响因子：
2
作者：
Czarnota J;Gennings C;Wheeler DC
通讯作者：
Wheeler DC
影响因子：
4.2
作者：
Emond, Jennifer A.;Karagas, Margaret R.;Gilbert-Diamond, Diane
通讯作者：
Gilbert-Diamond, Diane