Author:
Fei Dennis Liang,Koestler Devin C,Li Zhigang,Giambelli Camilla,Sanchez-Mejias Avencia,Gosse Julie A,Marsit Carmen J,Karagas Margaret R,Robbins David J
Abstract
Abstract
Background
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.
Methods
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.
Results
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).
Conclusions
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.
Publisher
Springer Science and Business Media LLC
Subject
Health, Toxicology and Mutagenesis,Public Health, Environmental and Occupational Health
Reference54 articles.
1. NRC: Arsenic in Drinking Water. 1999, Washington, DC: National Academy Press
2. IARC: Some drinking-water disinfectants and contaminants, including arsenic. IARC monographs on the evaluation of carcinogenic risks to humans. vol. 84. 2004, France: IARC Press, 37-270.
3. Vahter M: Effects of arsenic on maternal and fetal health. Annu Rev Nutr. 2009, 29: 381-399. 10.1146/annurev-nutr-080508-141102.
4. Ahmad SA, Sayed MH, Barua S, Khan MH, Faruquee MH, Jalil A, Hadi SA, Talukder HK: Arsenic in drinking water and pregnancy outcomes. Environ Health Perspect. 2001, 109: 629-631. 10.1289/ehp.01109629.
5. Rahman A, Vahter M, Ekstrom EC, Rahman M, Golam Mustafa AH, Wahed MA, Yunus M, Persson LA: Association of arsenic exposure during pregnancy with fetal loss and infant death: a cohort study in Bangladesh. Am J Epidemiol. 2007, 165: 1389-1396. 10.1093/aje/kwm025.
Cited by
71 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献