Transgenerational effects and mechanisms of nano-SiO₂ on pulmonary

Nanomaterials, such as nano-SiO₂, have been extensively studied and applied in various fields. However, little is known about the transgenerational effects of nano-SiO₂. The purpose of this study was to investigate the transgenerational effects and mechanisms of paternal nano-SiO₂ exposure on the lung of male offspring. Male C57BL/6 mice were exposed to nano-SiO₂, which were then mated with unexposed females to produce F1 and F2 generations. The effects of nano-SiO₂ were evaluated over two generations (F0 and F2) by determining pulmonary function, lung tissue pathology, and analyzing the imprinted gene expression and DNA methylation profile in lung tissues. The results showed that tidal volume (VT), 1/2 tidal volume flow (EF50), peak expiratory flow (PEF), peak inspiratory flow (PIF), and minute ventilation (MV) increased significantly in both the F0 and F2 generations. Moreover, HE staining of lung tissues showed inflammation of the F0. PCR results of lung tissues imply a significant change in the expression of Dlk1 and Dio3. Furthermore, nano-SiO₂ exposure increased the methylation levels of Dlk1 and Dio3 across generations F0 and F2. Overall, nano-SiO₂ exposure detrimentally impacts lung respiratory function in male mice by modulating the epigenetic regulation of Dlk1-Dio3 imprinted genes, potentially leading to transgenerational risks. However, further studies are needed to determine the long-term physiological consequences in adulthood.