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Neurotoxicol Teratol January 1, 2015; 47 102-13.

Methylmercury exposure during early Xenopus laevis development affects cell proliferation and death but not neural progenitor specification.

Huyck RW , Nagarkar M , Olsen N , Clamons SE , Saha MS .

Methylmercury (MeHg) is a widespread environmental toxin that preferentially and adversely affects developing organisms. To investigate the impact of MeHg toxicity on the formation of the vertebrate nervous system at physiologically relevant concentrations, we designed a graded phenotype scale for evaluating Xenopus laevis embryos exposed to MeHg in solution. Embryos displayed a range of abnormalities in response to MeHg, particularly in brain development, which is influenced by both MeHg concentration and the number of embryos per ml of exposure solution. A TC50 of ~50μg/l and LC50 of ~100μg/l were found when maintaining embryos at a density of one per ml, and both increased with increasing embryo density. In situ hybridization and microarray analysis showed no significant change in expression of early neural patterning genes including sox2, en2, or delta; however a noticeable decrease was observed in the terminal neural differentiation genes GAD and xGAT, but not xVGlut. PCNA, a marker for proliferating cells, was negatively correlated with MeHg dose, with a significant reduction in cell number in the forebrain and spinal cord of exposed embryos by tadpole stages. Conversely, the number of apoptotic cells in neural regions detected by a TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay was significantly increased. These results provide evidence that disruption of embryonic neural development by MeHg may not be directly due to a loss of neural progenitor specification and gene transcription, but to a more general decrease in cell proliferation and increase in cell death throughout the developing nervous system.

PubMed ID: 25496965
PMC ID: PMC4302163
Article link: Neurotoxicol Teratol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: dll1 en2 gad1.2 gnl3 pcna slc17a7 sox2

Article Images: [+] show captions
References [+] :
Amyot, Dark oxidation of dissolved and liquid elemental mercury in aquatic environments. 2005, Pubmed