Alteration of the glutamatergic system may be one mechanistic pathway. We aimed to determine whether mercury and seven OCs, including PCBs 138, 153, and 180, DDT and DDE, hexachlorobenzene (HCB), and beta-hexachlorocyclohexane (β-HCH) influence the cord levels of two excitatory amino acids, glutamate and aspartate. Secondly, we evaluated if this association was mediated by glutamate uptake measured in human placental membranes. The study sample included 40 newborns from a Spanish cohort selected according to cord mercury levels. We determined the content of both amino acids in cord blood samples by means of HPLC and assessed their associations with the contaminants using linear regression analyses, and the effect of the contaminants on glutamate uptake by means of [ 3 H]-aspartate binding in human placenta samples. PCB138, β-HCH, and the sum of the 3 PCBs and seven OCs showed a significant negative association with glutamate levels (decrease of 51, 24, 56 and 54 %, respectively, in glutamate levels for each 10-fold increase in the contaminant concentration). Mercury did not show a significant correlation neither with glutamate nor aspartate levels in cord blood, however a compensatory effect between THg and both PCB138, and 4,4'-DDE was observed. The organo-metallic derivative methylmercury completely inhibited glutamate uptake in placenta while PCB138 and β-HCH partially inhibited it (IC50 values: 4.9 ± 0.8 μM, 14.2± 1.2nM and 6.9± 2.9nM, respectively).We conclude that some environmental toxicants may alter the glutamate content in the umbilical cord blood, which might underlie alterations in human development.Key words: methylmercury, polychlorobiphenyl (PCB), organochlorine pesticides, placenta, umbilical cord blood, glutamate, transport, pollutants. 3 IntroductionSocial and economic development have been mediated by strong industrial growth involving the synthesis, use and release of large numbers of chemicals many of which are potentially harmful to human health and the environment (Li and Macdonald, 2005;Porta et al., 2012).Several of these chemicals, e.g. lead, mercury, polychlorinated biphenyls (PCBs), arsenic and toluene, have been associated to subclinical brain dysfunction and neurodevelopmental disorders such as poorer cognitive and motor development, attention deficit, hyperactivity, and sensory deficits but the underlying processes leading to these effects are still unknown (Grandjean and Landrigan, 2006). Pollutants come from several different sources, move on the environment and eventually accumulate in the food chain. Daily exposure to environmental persistent pollutants results in detectable levels of metals, PCBs and organochlorine pesticides in woman bodies (Woodruff et al., 2011). During pregnancy, the pollutants accumulated by the women can reach the fetus crossing the placenta. Although the placenta regulates the exchange of nutrients and oxygen between mother and fetus and acts as a barrier of many toxicants, it does not provide protection against certain environmental contaminants (Proui...

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