Expression of the sFLT1 gene in cord blood cells is associated to maternal arsenic exposure and decreased birth weight

PLoS One. 2014 Mar 24;9(3):e92677. doi: 10.1371/journal.pone.0092677. eCollection 2014.

Abstract

There is increasing epidemiologic evidence that arsenic exposure in utero is associated with adverse pregnancy outcomes and may contribute to long-term health effects. These effects may occur at low environmental exposures but the underlying molecular mechanism is not clear. We collected cord blood samples of 183 newborns to identify associations between arsenic levels and birth anthropometric parameters in an area with very low arsenic exposure. Our core research aim was to screen for transcriptional marks that mechanistically explain these associations. Multiple regression analyses showed that birth weight decreased with 47 g (95% CI: 16-78 g) for an interquartile range increase of 0.99 μg/L arsenic. The model was adjusted for child's sex, maternal smoking during pregnancy, gestational age, and parity. Higher arsenic concentrations and reduced birth weight were positively associated with changes in expression of the sFLT1 (soluble fms-like tyrosine kinase-1) gene in cord blood cells in girls. The protein product of sFLT1 is a scavenger of vascular endothelial growth factor (VEGF) in the extracellular environment and plays a key role in the inhibition of placental angiogenesis. In terms of fetal development, inhibition of placental angiogenesis leads to impaired nutrition and hence to growth retardation. Various genes related to DNA methylation and oxidative stress showed also changed expression in relation to arsenic exposure but were not related to birth outcome parameters. In conclusion, this study suggests that increased expression of sFLT1 is an intermediate marker that points to placental angiogenesis as a pathway linking prenatal arsenic exposure to reduced birth weight.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arsenic / blood
  • Arsenic / toxicity*
  • Birth Weight / drug effects
  • Birth Weight / genetics*
  • Cohort Studies
  • DNA Methylation / drug effects
  • DNA Methylation / genetics
  • Female
  • Fetal Blood / drug effects
  • Fetal Blood / metabolism*
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Humans
  • Infant, Newborn
  • Male
  • Maternal Exposure / adverse effects*
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Pregnancy
  • Vascular Endothelial Growth Factor Receptor-1 / blood*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics*

Substances

  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • Arsenic

Grants and funding

The studies of the Flemish Center of Expertise on Environment and Health were commissioned, financed and steered by the Ministry of the Flemish Community (Department of Economics, Science and Innovation; Flemish Agency for Care and Health; and Department of Environment, Nature and Energy). The research received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement OBELIX 227391. Isabelle Sioen is financially supported by the Research Foundation - Flanders (Grant n°: 1.2.683.11.N.00). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.