Abstract
BackgroundLead (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 from 99 women enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort 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 using multiple linear regression models. Class- and pathway-based 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 tibia and patella, were 2.5 (7.3) µg/g and 3.6 (9.5) µg/g, respectively. Of 215 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 8 metabolites, respectively (p < 0.05). Comparing results from bone and blood Pb, glycochenodeoxycholic acid, glycocholic acid, and 1-arachidonoylglycerol were positively associated with blood Pb and tibia Pb, and 7-methylguanine was negatively associated with blood Pb and patella Pb. One metabolite, 5-aminopentanoic acid, was negatively associated with all three Pb measures.ConclusionsThis study identified serum metabolites in pregnant women associated with Pb measured in blood and bone. These findings provide insights on the metabolic profile around Pb exposure in pregnancy and information to guide mechanistic studies of toxicological effects for mothers and children.
Highlights
Lead (Pb) exposure is a global health hazard causing a wide range of adverse health outcomes
Current guidelines for medical management of Pb-exposed adults recommend that pregnant women avoid occupations and avocational exposures that may result in blood Pb levels >5 μg/dL [31]
Our results show that cumulative Pb exposures measured in bone reflected different metabolite association patterns than acute Pb exposures measured in third-trimester serum (Tables 1 and 2)
Summary
Lead (Pb) exposure is a global health hazard causing a wide range of adverse health outcomes. 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. Lead (Pb) exposure is a persistent global health hazard, with no safe exposure threshold [1]. There are multiple critical neurodevelopmental windows during childhood wherein Pb exposure may lead to life-long adverse neurological effects [8, 9]. Despite these significant health concerns, the mechanisms of Pb toxicity are not fully understood. Further examination of Pb exposure during pregnancy is crucial, as exposure during this period can exert harmful effects in both mothers and children
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