Department of Surgery, Molecular Oncology Program, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Environ Health. 2013 Jul 16;12:58. doi: 10.1186/1476-069X-12-58.
Epidemiologic studies and animal models suggest that in utero arsenic exposure affects fetal health, with a negative association between maternal arsenic ingestion and infant birth weight often observed. However, the molecular mechanisms for this association remain elusive. In the present study, we aimed to increase our understanding of the impact of low-dose arsenic exposure on fetal health by identifying possible arsenic-associated fetal tissue biomarkers in a cohort of pregnant women exposed to arsenic at low levels.
Arsenic concentrations were determined from the urine samples of a cohort of 133 pregnant women from New Hampshire. Placental tissue samples collected from enrollees were homogenized and profiled for gene expression across a panel of candidate genes, including known arsenic regulated targets and genes involved in arsenic transport, metabolism, or disease susceptibility. Multivariable adjusted linear regression models were used to examine the relationship of candidate gene expression with arsenic exposure or with birth weight of the baby.
Placental expression of the arsenic transporter AQP9 was positively associated with maternal urinary arsenic levels during pregnancy (coefficient estimate: 0.25; 95% confidence interval: 0.05 - 0.45). Placental expression of AQP9 related to expression of the phospholipase ENPP2 which was positively associated with infant birth weight (coefficient estimate: 0.28; 95% CI: 0.09 - 0.47). A structural equation model indicated that these genes may mediate arsenic's effect on infant birth weight (coefficient estimate: -0.009; 95% confidence interval: -0.032 - -0.001; 10,000 replications for bootstrapping).
We identified the expression of AQP9 as a potential fetal biomarker for arsenic exposure. Further, we identified a positive association between the placental expression of phospholipase ENPP2 and infant birth weight. These findings suggest a path by which arsenic may affect birth outcomes.
流行病学研究和动物模型表明，胎儿在子宫内暴露于砷会影响其健康，而母体摄入砷与婴儿出生体重之间往往存在负相关关系。然而，这种关联的分子机制仍不清楚。本研究旨在通过鉴定低水平砷暴露孕妇队列中可能与砷相关的胎儿组织生物标志物，增加对低剂量砷暴露对胎儿健康影响的认识。
从新罕布什尔州的 133 名孕妇的尿样中测定砷浓度。从入组者中收集胎盘组织样本，对候选基因进行基因表达谱分析，包括已知的砷调节靶基因和参与砷转运、代谢或疾病易感性的基因。采用多变量调整线性回归模型，检验候选基因表达与砷暴露或婴儿出生体重的关系。
胎盘砷转运体 AQP9 的表达与孕妇妊娠期间尿砷水平呈正相关（系数估计值：0.25；95%置信区间：0.05-0.45）。AQP9 与磷脂酶 ENPP2 的表达相关，而 ENPP2 与婴儿出生体重呈正相关（系数估计值：0.28；95%置信区间：0.09-0.47）。结构方程模型表明，这些基因可能介导砷对婴儿出生体重的影响（系数估计值：-0.009；95%置信区间：-0.032-0.001；bootstrap 10000 次重复）。
我们确定 AQP9 的表达是砷暴露的潜在胎儿生物标志物。此外，我们发现胎盘 ENPP2 表达与婴儿出生体重呈正相关。这些发现表明了砷可能影响出生结局的途径。
