Lead exposure and serum metabolite profiles in pregnant women in Mexico City

Abstract

AbstractBackgroundLead (Pb) exposure is a global health hazard causing a wide range of adverse health outcomes. Yet, the mechanisms of Pb toxicology remain incompletely understood, especially during pregnancy. To uncover biological pathways impacted by Pb exposure, this study investigated serum metabolomic profiles during the third trimester of pregnancy that are associated with blood Pb and bone Pb.MethodsWe used data and specimens collected from 99 women enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort based in Mexico City. Maternal Pb exposure was measured in whole blood samples from the third trimester of pregnancy and in the tibia and patella bones at 1 month postpartum. Third-trimester serum samples underwent metabolomic analysis; metabolites were identified based on matching to an in-house analytical standard library. A metabolome-wide association study was performed with all three Pb measurements using multiple linear regression models, adjusted for confounders and batch effects. Class enrichment analyses were also conducted.ResultsThe median (interquartile range) blood Pb concentration was 2.9 (2.6) μg/dL. Median bone Pb, measured in the patella and tibia, were 2.5 (7.3) μg/g and 3.6 (9.5) μg/g, respectively. Of 248 total metabolites identified in serum, 31 were associated with blood Pb (p<0.05). Class enrichment analysis identified significant overrepresentation of metabolites classified as fatty acids and conjugates, amino acids and peptides, and purines. Tibia and patella Pb were associated with 14 and 11 metabolites, respectively (p<0.05). Comparing results from bone and blood Pb, glycochenodeoxycholic acid and glycocholic acid were negatively associated with blood Pb and tibia Pb, while 5-aminopentanoic acid and 7-methylguanine were negatively associated with blood Pb and patella Pb. One metabolite, 5-aminopentanoic acid, was associated with all three Pb measures.ConclusionThis study identified serum metabolites in pregnant women associated with Pb measured in blood (31 metabolites) and bone (tibia: 14 metabolites, patella: 11 metabolites). These findings provide insights on the metabolic profile around Pb exposure in pregnancy and may provide important links to guide detailed studies of toxicological effects for both mothers and children.