Maternal Iron Deficiency and Environmental Lead (Pb) Exposure Alter the Predictive Value of Blood Pb Levels on Brain Pb Burden in the Offspring in a Dietary Mouse Model: An Important Consideration for Cumulative Risk in Development

母体缺铁和环境铅 (Pb) 暴露会改变膳食小鼠模型中血铅水平对后代脑铅负担的预测价值:发育累积风险的重要考虑因素

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作者:Janine Cubello, Derick R Peterson, Lu Wang, Margot Mayer-Proschel

Abstract

Maternal iron deficiency (ID) and environmental lead (Pb) exposure are co-occurring insults that both affect the neurodevelopment of offspring. Few studies have investigated how ID affects brain-region-specific Pb accumulations using human-relevant Pb concentrations. Furthermore, how these Pb exposures impact blood and brain Fe levels remains unclear. Importantly, we also wanted to determine whether the use of blood Pb levels as a surrogate for the brain Pb burden is affected by underlying iron status. We exposed virgin Swiss Webster female mice to one of six conditions differing by iron diet and Pb water concentration (0 ppm, 19 ppm, or 50 ppm lead acetate) and used Inductively Coupled Plasma Mass Spectrometry to measure the maternal and offspring circulating, stored, and brain Pb levels. We found that maternal ID rendered the offspring iron-deficient anemic and led to a region-specific depletion of brain Fe that was exacerbated by Pb in a dose-specific manner. The postnatal iron deficiency anemia also exacerbated cortical and hippocampal Pb accumulation. Interestingly, BPb levels only correlated with the brain Pb burden in ID pups but not in IN offspring. We conclude that ID significantly increases the brain Pb burden and that BPb levels alone are insufficient as a clinical surrogate to make extrapolations on the brain Pb burden.

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