Aluminum exposure disturbs epigenetic modification and organelle function during early embryo development

Aluminum is a lightweight and corrosion-resistant metal element that is widely used in industries, construction, food, and pharmaceuticals, and it can adversely affect multiple organ systems including the nervous system, skeletal system, reproductive system, blood system, and immune system. In present study, we investigated the effects of aluminum exposure on mammalian embryo development. Our data demonstrate that aluminum exposure induces mouse early embryo development defects, including those at the zygotes and 2-cell stages, causing a decrease in general transcription activity. We found mitochondrial dysfunction and a significant increase in reactive oxygen species (ROS) levels, thereby triggering oxidative stress, and this oxidative stress subsequently results in DNA damage. Additionally, we observed substantial alterations in histone modification levels, specifically H3K4me2, H3K4me3, H3K27me3, and H4K12ac. These changes in histone modifications were found to be closely associated with the observed DNA damage and mitochondrial dysfunction. We also observed aberrant distribution of lysosomes, endoplasmic reticulum, and Golgi apparatus, indicating that aluminum could disturb protein modification and transport in embryos. In conclusion, our results indicated that aluminum exposure disrupted early embryo development by inducing mitochondria-based oxidative stress, which further caused DNA damage, aberrant histone modifications and organelle functions in mouse embryos.