Autism has been associated with epigenetic changes: Tiny chemical tags in the regulatory regions of genes that affect how genes express themselves by turning them on or off. One gene often decreased in expression in the brain tissue of autistic individuals is MECP2, a gene that governs the expression of genes crucial to brain development. Exposure to environmental pollutants is also thought to play a role in autism. These two phenomena both involve a small cellular organ called mitochondria. The suspect environmental pollutants are toxic to mitochondria, which play a critical role in epigenetics: Pollution exposure can lower the amount of mitochondrial DNA (mtDNA) in a cell, causing an increase in placement of epigenetic tags by DNMT1 that leads to gene silencing. We hypothesize that exposure during pregnancy to pollutants toxic to mitochondria causes a decrease in mtDNA copy number and increased placement of epigenetic tags by DNMT1 on key developmental genes, affecting pathways that have direct roles in the development of autism. We will expose mice, during pregnancy, to selected toxicants and evaluate adult behavior and associated biochemical changes in brain tissue. Valproic acid will be used as a positive control, with saline as a negative control. The environmental pollutants lead, arsenic, cadmium, manganese, mercury, and permethrin will be investigated for their potential to induce autistic behavior changes. Brain tissue will then be used for molecular studies of mtDNA copy number, expression of DNMT1, and alterations to the epigenome on both a genomewide and gene-specific level.