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Characterization of placental cholinesterases and activity induction associated to environmental organophosphate exposure.

ABSTRACT: Although non-innervated, the placenta contains both cholinesterases (ChEs), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). These enzymes are well-known for their multiple molecular forms. In a first approach, we used recognized specific inhibitors, substrate preferences and non-denaturating gel electrophoresis in order to characterize the ChE profile of term placenta from uncomplicated pregnancy. Results strongly suggest that the predominant cholinesterasic form present was tetrameric BChE. It is well established that both ChEs are targets of cholinesterase-inhibiting organophosphates (OP), one of the most important classes of chemicals actively applied to the environment. However, we have previously reported increased ChEs activity in placenta of rural residents exposed to OP. In the present work, we have studied: 1) whether this finding was reproducible and, 2) whether AChE or BChE up regulation is behind the increase of placental ChE activity. The population studied included forty healthy women who live in an agricultural area. Samples were collected during both the OP pulverization period (PP) and the recess period (RP). The placental ChEs activity increased in PP, evidencing reproducibility of previous results. The analysis of non-denaturating gels revealed that increased activity of total ChE activity in placenta from women exposed to OP may be attributable to tetrameric BChE up-regulation.

SUBMITTER: Sanchez S

PROVIDER: S-EPMC5598449 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Characterization of placental cholinesterases and activity induction associated to environmental organophosphate exposure.

Sánchez S S Vera B B Montagna C C Magnarelli G G

Toxicology reports 20141129

Although non-innervated, the placenta contains both cholinesterases (ChEs), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). These enzymes are well-known for their multiple molecular forms. In a first approach, we used recognized specific inhibitors, substrate preferences and non-denaturating gel electrophoresis in order to characterize the ChE profile of term placenta from uncomplicated pregnancy. Results strongly suggest that the predominant cholinesterasic form present was tetram ...[more]

PMID: 28962379

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Project description:Psychoactive pharmaceuticals have been found as teratogens at clinical dosage during pregnancy. These pharmaceuticals have also been detected in minute (ppb) concentrations in drinking water in the US, and are environmental contaminants that may be complicit in triggering neurological disorders in genetically susceptible individuals. Previous studies have determined that psychoactive pharmaceuticals (fluoxetine, venlafaxine and carbamazepine) at environmentally relevant concentrations enriched sets of genes regulating development and function of the nervous system in fathead minnows. Altered gene sets were also associated with potential neurological disorders, including autism spectrum disorders (ASD). Subsequent in vitro studies indicated that psychoactive pharmaceuticals altered ASD-associated synaptic protein expression and gene expression in human neuronal cells. However, it is unknown if environmentally relevant concentrations of these pharmaceuticals are able to cross biological barriers from mother to fetus, thus potentially posing risks to nervous system development. The main objective of this study was to test whether psychoactive pharmaceuticals (fluoxetine, venlafaxine, and carbamazepine) administered through the drinking water at environmental concentrations to pregnant mice could reach the brain of the developing embryo by crossing intestinal and placental barriers. We addressed this question by adding (2)H-isotope labeled pharmaceuticals to the drinking water of female mice for 20 days (10 pre-and 10 post-conception days), and quantifying (2)H-isotope enrichment signals in the dam liver and brain of developing embryos using isotope ratio mass spectrometry. Significant levels of (2)H enrichment was detected in the brain of embryos and livers of carbamazepine-treated mice but not in those of control dams, or for fluoxetine or venlafaxine application. These results provide the first evidence that carbamazepine in drinking water and at typical environmental concentrations is transmitted from mother to embryo. Our results, combined with previous evidence that carbamazepine may be associated with ASD in infants, warrant the closer examination of psychoactive pharmaceuticals in drinking water and their potential association with neurodevelopmental disorders.

Dataset Information

Characterization of placental cholinesterases and activity induction associated to environmental organophosphate exposure.

Publications

Characterization of placental cholinesterases and activity induction associated to environmental organophosphate exposure.

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