Global Screening of Human Cord Blood Proteomes for Biomarkers of Toxic Exposure and Effect

BACKGROUND: Exposures of pregnant women to natural and manmade chemicals can lead to negative health effects in the baby, ranging from low birth weight to developmental defects. In some cases, diseases were postulated to have their basis in toxic exposure in utero or in early childhood. Therefore, an understanding of fetal responses to environmental exposures is essential. To that end, cord blood is a readily accessible biofluid whose proteomic makeup remains mostly unexplored when compared with that of adults. OBJECTIVES: Our goal was an initial global assessment of the fetal serum proteome and for the identification of protein biomarkers indicative of toxic in utero exposures related to maternal cigarette smoking. METHODS: Drawing from a repository of 300 samples, we selected umbilical cord blood sera from 12 babies born to six smokers and six nonsmokers and analyzed both sample pools by tandem mass spectrometry in conjunction with isobaric tags (iTRAQ) for protein quantification. RESULTS: We identified 203 proteins, 17 of which were differentially expressed between the cigarette smoke–exposed and control populations. Most of the identified candidate biomarkers were biologically plausible, thereby underscoring the feasibility of screening neonates with global proteomic techniques for biomarkers of exposure and early biological effects triggered by in utero chemical exposures. CONCLUSIONS: This validation study provides an initial view of the proteome of human cord blood sera; it demonstrates the feasibility of identifying therein by use of proteomics, biomarkers of environmental, toxic exposures.