Association between in Utero arsenic exposure, placental gene expression, and infant birth weight: A US birth cohort study

Dennis Liang Fei, Devin C. Koestler, Zhigang Li, Camilla Giambelli, Avencia Sanchez-Mejias, Julie A. Gosse, Carmen J. Marsit, Margaret R. Karagas, David J Robbins

Research output: Contribution to journalArticle

50 Citations (Scopus)

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.

Original languageEnglish
Article number58
JournalEnvironmental Health: A Global Access Science Source
Volume12
Issue number1
DOIs
StatePublished - Aug 12 2013

Fingerprint

Arsenic
Birth Weight
Cohort Studies
Parturition
Gene Expression
Phospholipases
Pregnant Women
Linear Models
Biomarkers
Mothers
Confidence Intervals
Genes
Structural Models
Disease Susceptibility
Health
Epidemiologic Studies
Fetus
Animal Models
Eating

Keywords

  • AQP9
  • Arsenic
  • Biomarker
  • Birth weight
  • ENPP2
  • Placenta

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

Cite this

Association between in Utero arsenic exposure, placental gene expression, and infant birth weight : A US birth cohort study. / 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.

In: Environmental Health: A Global Access Science Source, Vol. 12, No. 1, 58, 12.08.2013.

Research output: Contribution to journalArticle

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. / Association between in Utero arsenic exposure, placental gene expression, and infant birth weight : A US birth cohort study. In: Environmental Health: A Global Access Science Source. 2013 ; Vol. 12, No. 1.
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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.",
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AU - Fei, Dennis Liang

AU - Koestler, Devin C.

AU - Li, Zhigang

AU - Giambelli, Camilla

AU - Sanchez-Mejias, Avencia

AU - Gosse, Julie A.

AU - Marsit, Carmen J.

AU - Karagas, Margaret R.

AU - Robbins, David J

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N2 - 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.

AB - 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.

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