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J Toxicol Sci. 2012;37(6):1247-52.

Effect of fetal exposure to titanium dioxide nanoparticle on brain development - brain region information.

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Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan.


The production of man-made nanoparticles is increasing in nanotechnology, and health effect of nanomaterials is of concern. We previously reported that fetal exposure to titanium dioxide (TiO(2)) affects the brain of offspring during the perinatal period. The aim of this study was to extract candidate brain regions of interest using a specific group of Medical Subject Headings (MeSH) from a microarray dataset of the whole brain of mice prenatally exposed to TiO(2) nanoparticle. After subcutaneous injection of TiO(2) (total 0.4 mg) into pregnant mice on gestational days 6-15, brain tissues were collected from male fetuses on embryonic day 16 and from male pups on postnatal days 2, 7, 14 and 21. Gene expression changes were determined by microarray and analyzed with MeSH indicating brain regions. As a result, a total of twenty-one MeSH were significantly enriched from gene expression data. The results provide data to support the hypothesis that prenatal TiO(2) exposure results in alteration to the cerebral cortex, olfactory bulb and some regions intimately related to dopamine systems of offspring mice. The genes associated with the striatum were differentially expressed during the perinatal period, and those associated with the regions related to dopamine neuron system and the prefrontal region were dysregulated in the later infantile period. The anatomical information gave us clues as to the mechanisms that underlie alteration of cerebral gene expression and phenotypes induced by fetal TiO(2) exposure.

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