title: Expression of the sFLT1 gene in cord blood cells is associated to maternal arsenic exposure and decreased birth weight.
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.
authors.affiliation: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Remy
authors.affiliation: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Govarts
authors.affiliation: Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Diepenbeek, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Bruckers
authors.affiliation: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
authors.forename: Melissa
authors.initials: M
authors.lastname: Paulussen
authors.affiliation: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Britt
authors.initials: B
authors.lastname: Wens
authors.affiliation: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
authors.forename: Elly Den
authors.initials: ED
authors.lastname: Hond
authors.affiliation: Department of Health, Provincial Institute for Hygiene, Antwerp, Belgium.
authors.forename: Vera
authors.initials: V
authors.lastname: Nelen
authors.affiliation: Department of Analytical, Environmental and Geochemistry (AEGC), Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Willy
authors.initials: W
authors.lastname: Baeyens
authors.affiliation: Department of Analytical, Environmental and Geochemistry (AEGC), Vrije Universiteit Brussel, Brussels, Belgium; Department of Radiotherapy and Experimental cancer research, Ghent University, Ghent, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: van Larebeke
authors.affiliation: Department Sociology, Faculty of Political and Social Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Loots
authors.affiliation: Department of Public Health, Ghent University, Ghent, Belgium; FWO Research Foundation, Brussels, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sioen
authors.affiliation: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Environmental Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Greet
authors.initials: G
authors.lastname: Schoeters
mesh_terms: D001151:Arsenic / Q000097:blood / Q000633:toxicity*; D001724:Birth Weight / Q000187:drug effects / Q000235:genetics*; D015331:Cohort Studies; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005312:Fetal Blood / Q000187:drug effects / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D011247:Pregnancy; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood* / Q000235:genetics*
chemical_list: C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D001151:Arsenic