title: Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling.
abstract: 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 Gómez 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 μg 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.
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Bailey
authors.forename: Jessica
authors.initials: J
authors.lastname: Laine
authors.forename: Julia E
authors.initials: JE
authors.lastname: Rager
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sebastian
authors.forename: Andrew
authors.initials: A
authors.lastname: Olshan
authors.forename: Lisa
authors.initials: L
authors.lastname: Smeester
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Drobná
authors.forename: Miroslav
authors.initials: M
authors.lastname: Styblo
authors.forename: Marisela
authors.initials: M
authors.lastname: Rubio-Andrade
authors.forename: Gonzalo
authors.initials: G
authors.lastname: García-Vargas
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
mesh_terms: D001151:Arsenic / Q000633:toxicity* / Q000652:urine; D060766:Drinking Water / Q000032:analysis / Q000592:standards; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D008800:Mexico; D015999:Multivariate Analysis; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D012044:Regression Analysis; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000633:toxicity* / Q000652:urine
chemical_list: D060766:Drinking Water; D020543:Proteome; D014409:Tumor Necrosis Factor-alpha; D014874:Water Pollutants, Chemical; D001151:Arsenic
keywords: arsenic; arsenic metabolism; birth outcomes; in utero; metals; pregnancy