Maternal exposure to sunlight-irradiated graphene oxide induces neurodegeneration-like symptoms in zebrafish offspring through intergenerational translocation and genomic DNA methylation alterations

The physiochemical properties of graphene oxide may be affected by sunlight irradiation. However, the underlying mechanisms that alter the properties and subsequent intergenerational effects are not sufficiently investigate. Epigenetics is an early sensitive marker for the intergenerational effects of nanomaterial exposure due to the epigenetic memory. In this study, we investigate changes in the physicochemical properties and the intergenerational effects of maternal exposure to simulated sunlight-irradiated polyethyleneimine-functionalized graphene oxide (SL-PEI-GO). Results show that the physicochemical properties of polyethyleneimine-functionalized graphene oxide (PEI-GO) can be altered significantly by the oxidation of carbon atoms with unpaired electrons present in the defects and on the edges of PEI-GO by sunlight. First, the positive charges, sharp edges, defects and disordered structures of SL-PEI-GO make it translocate from maternal zebrafish to offspring, thus catalyzing the production of reactive oxygen species and damaging mitochondria directly. In addition, changes in DNA methylation reduce the expression of protocadherin1a, protocadherin19 and cadherin4, thus destroying cell membrane integrity, cell adhesion and Ca2+ binding. The alteration of DNA methylation induced by maternal exposure activates the Ca2+-CaMKK-brsk2a pathway, which catalyzes the phosphorylation of Tau and eventually results in the appearance of neurodegeneration-like symptoms, including the loss of neurons and neurobehavioral disorders. This study demonstrates that maternal exposure to SL-PEI-GO induces clear neurodegeneration-like symptoms in offspring through both the intergenerational translocation of nanomaterials and differential DNA methylation. These findings may provide new insights into the health risks of nanomaterials altered by nature conditions.