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

Abstract

BackgroundExposures 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.ObjectivesOur 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.MethodsDrawing 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.ResultsWe 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.ConclusionsThis 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.

The human placental proteome is affected by maternal smoking

“…Similarly, placentae from severe preeclamptic mothers have demonstrated comparable decrease in haemoglobin–β-chain levels [27]. In contrast, HBB, HBA and HBG levels were significantly elevated in proteomic studies of: (i) cord blood from maternal smokers [33] and (ii) the effects of growth restriction on the human placenta [30]. Carbonic anhydrases are key components in transporting carbon dioxide from tissues to circulation, and maintaining the acid-base balance in tissues.…”

Analysis of the plasma proteome using iTRAQ and TMT‐based Isobaric labeling

“…Several of the differentially expressed proteins were already associated with tobacco related diseases, including lung cancer and chronic obstructive pulmonary disease . Colquhoun et al investigated the effect of smoking on maternal serum from cord blood . Although cord blood serum can be richer in intracellular proteins and more varied than matured serum, the study was conducted with older MS instrumentation (Applied Biosystems, QSTAR‐Pulsar) and they reported quantification of in the order of 200 proteins.…”

“…As well as mapping the changes in maternal serum during pregnancy, the iTRAQ method has also been used to study complications during pregnancy, such as preeclampsia and intra‐uterine growth restriction, in addition to evaluating the effects of smoking on the cord blood serum proteome . Auer and co‐workers used iTRAQ to compare the plasma of women with preeclampsia and/or intra‐uterine growth restriction with healthy controls (∼40 subjects in total).…”

“…Among the studies of respiratory afflictions, researchers have considered asthma, 130 acute respiratory syndrome 59 133 Colquhoun et al investigated the effect of smoking on maternal serum from cord blood. 134 Although cord blood serum can be richer in intracellular proteins and more varied than matured serum, the study was conducted with older MS instrumentation (Applied Biosystems, QSTAR-Pulsar) and they reported quantification of in the order of 200 proteins. Other studies of respiratory afflictions have included tuberculosis [135][136][137][138] and Mycoplasma pneumoniae (MP) infections 139 (see below).…”

“…Isobaric labeling has been used to study the plasma proteome in the context of gynecological health, including the study of endometriosis, adenomyosis, endometrial hyperplasia and gestational diabetes (Table 5B) As well as mapping the changes in maternal serum during pregnancy, 163 the iTRAQ method has also been used to study complications during pregnancy, such as preeclampsia and intrauterine growth restriction, [164][165][166] in addition to evaluating the effects of smoking on the cord blood serum proteome. 134 Auer and coworkers used iTRAQ to compare the plasma of women with preeclampsia and/or intra-uterine growth restriction with healthy controls (∼40 subjects in total). Among the proteins differentially expressed with intra-uterine growth restriction were those from the complement and coagulation cascades.…”