Prenatal Arsenic Exposure and Shifts in the Newborn Proteome: Interindividual Differences in Tumor Necrosis Factor (TNF)-Responsive Signaling

Editor's Highlight: Babies, infants and young children are not just small adults; their physiology and biochemistry differs in countless ways creating a need for research on this vulnerable population. But such research poses numerous ethical and moral challenges. The acquisition of umbilical cord blood provides an opportunity to assess the newborn's environment without risk to the child. In this issue of the Journal, Bailey and coworkers used antibody arrays to examine protein profiles in umbilical cord blood and compared it to levels of arsenic in the mothers' urine and drinking water. The study population was based in G'omez Palacio, Mexico, where arsenic levels are well above regulatory guidelines. Protein network analysis revealed several proteins involved in tumor necrosis factor signaling were elevated in the offspring of highly exposed mothers, suggesting that elevated arsenic induces widespread inflammatory signaling. Such markers could ultimately be used to assess the impact of arsenic exposure in this and other vulnerable populations and may lead to mechanisms whereby arsenic exposure in utero contributes to adverse outcomes later in life. -Gary W. Miller and Ronald N. Hines.Exposure to inorganic arsenic (iAs) early in life is associated with adverse health effects in infants, children, and adults, and yet the biological mechanisms that underlie these effects are understudied. The objective of this research was to examine the proteomic shifts associated with prenatal iAs exposure using cord blood samples isolated from 50 newborns from G<remove>mez Palacio, Mexico. Levels of iAs in maternal drinking water (DW-iAs) and the sum of iAs and iAs metabolites in maternal urine (U-tAs) were determined. Cord blood samples representing varying iAs exposure levels during the prenatal period (DW-iAs ranging from < 1 to 236 mu g As/l) were analyzed for altered expression of proteins associated with U-tAs using a high throughput, antibody-based method. A total of 111 proteins were identified that had a significant association between protein level in newborn cord blood and maternal U-tAs. Many of these proteins are regulated by tumor necrosis factor and are enriched in functionality related to immune/inflammatory response and cellular development/proliferation. Interindividual differences in proteomic response were observed in which 30 newborns were "activators," displaying a positive relationship between protein expression and maternal U-tAs. For 20 "repressor" newborns, a negative relationship between protein expression level and maternal U-tAs was observed. The activator/repressor status was significantly associated with maternal U-tAs and head circumference in newborn males. These results may provide a critical groundwork for understanding the diverse health effects associated with prenatal arsenic exposure and highlight interindividual responses to arsenic that likely influence differential susceptibility to adverse health outcomes.