Mouse whole brain: Alteration of DNA methylation status caused by prenatal titanium dioxide nanoparticle exposure

Reportedly, titanium dioxide nanoparticle exposure during pregnancy can affect the development of the central nervous system in mouse offspring; however, the underlying mechanism remains unknown. In the present study, we investigated the impact of prenatal dioxide nanoparticle exposure on global DNA methylation in the brains of neonatal mice. Pregnant C57BL/6J mice were intratracheally administered a dioxide nanoparticle suspension (100 ug/mouse) on gestational day 10.5, and brains were collected from male and female offspring at day 1 postpartum. After extraction of methylated DNA by immunoprecipitation, the DNA methylation profile was analyzed using a mouse CpG island microarray. Among genes in the CpG island microarray, DNA methylation was increased in 614 and 2924 genes and decreased in 6219 and 6463 genes in male and female offspring, respectively. Combined with mRNA microarray analysis, 88 and 89 genes were upregulated (≥ 1.5-fold) accompanied by demethylation of CpG islands, whereas 13 and 33 genes were downregulated (≤ 0.67-fold) accompanied by demethylation of CpG islands in male and female offspring mice, respectively. Gene Set Enrichment Analysis (GSEA) revealed that these genes were enriched in gene ontology terms related to the regulation of transcription factors, cell proliferation, and organism development. Additionally, MeSH terms related to stem cells and morphogenesis were enriched. Alteration of DNA methylation status caused by prenatal titanium dioxie nanoparticle exposure (GD14: 100 ug/mouse) in mouse brain was analyzed. Brains were collected from male and female offspring at day 1 postpartum and DNA methylation profiles were analyzed (Vehicle vs. titanium nanoparticle; both male and female).