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.

A repeated measures microarray design with 22 healthy, non-smoking volunteers (aging 32±5years) was set up to study transcriptome profiles in whole blood samples. The results indicate that repeatable data can be obtained with high within-subject correlation. Probes that could discriminate between individuals are associated with immune and inflammatory functions. When investigating possible time trends in the microarray data, we have found no differential expression within a sampling period (within-season effect). Differential expression was observed between sampling seasons and the data suggest a weak response of genes related to immune system functioning. Finally, a high number of probes showed significant season-specific expression variability within subjects. Expression variability increased in springtime and there was an association of the probe list with immune system functioning. Our study suggests that the blood transcriptome of healthy individuals is reproducible over a time period of several months.

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