Abstract
BackgroundEpidemiologic 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.MethodsArsenic 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.ResultsPlacental 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).ConclusionsWe 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.
Highlights
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
To explore the mechanism by which arsenic exposure might influence birth weight, we examined the association between expression of our panel of candidate placental genes and infant birth weight
Using placenta as the source of fetal tissue from a US cohort exposed to arsenic around the maximum contaminant level (MCL), we identified the arsenic transporter AQP9 as a possible biomarker of arsenic exposure in fetal tissues
Summary
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. We recently reported that food sources, such as rice, can contribute in exposing pregnant women to arsenic [17] This finding, coupled with elevated arsenic levels detected in infant food [18,19,20], has raised serious public health and scientific concerns regarding the potential for relatively common fetal/early childhood exposure to arsenic. We sought to develop such biomarkers, identifying relevant genes associated with low-dose arsenic exposure in an area of United States (New Hampshire) where a cohort of pregnant women used private wells with arsenic both above and below the current drinking water maximum contaminant level (MCL) of 10 μg/L [2]. We subsequently associated the expression of these biomarkers to infant birth weight to provide insight into the mechanisms underlying the adverse effect of in utero arsenic exposure on infant health
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