Effect of Nano-SiO2 on Expression and Aberrant Methylation of Imprinted Genes in Lung and Testis.

ABSTRACT

Nanotechnology has been developing rapidly and is now used in many cutting-edge medical therapeutics. However, there is increasing concern that exposure to nanoparticles (NPs) may induce different systemic diseases as epigenetic mechanisms are associated with more and more disease. The role of NP epigenomic modification is important to disease etiology. Our study aimed to determine the epigenetic mechanisms of damage in lung and testis cells by exposing cells to SiO2 NPs. We used male C57BL/6 mice to characterize the damaging effect of SiO2 NPs on lung and testis cells as well as the resulting methylation state at the imprinted Dlk1/Dio3 domain region. The A549 cells exposed to SiO2 NPs had cell apoptosis, and male mice exposed to SiO2 NPs had altered lung and testis tissues. The genes in the imprinted domains Dlk1/Dio3 region changed in both tissues; Dlk1, Rtl1, and Dio3 are upregulated in testis while Dlk1 and Dio3 are also upregulated in lung tissues. Bisulfite sequencing PCR of male adult lung and testis were mostly hypomethylated, with a few hypermethylated CpGs. These findings indicate that nanoparticles play an important role in DNA methylation of imprinted genes.