Increasing numbers of children are being diagnosed with autism spectrum disorders (ASD and relatedneurobehavioral disorders. Based on the rising incidence that is not explained by genetics alone, it has beenpostulated that in utero exposure to environmental chemicals may increase the risk for these disorders.Perinatal exposure of children through the mother to endocrine disrupting chemicals (EDCs), includingbisphenol A (BPA), has been linked to ASD. To establish potential causation and underlying mechanisms,it is important to test these chemicals in a relevant animal model species, where the clinical corebehavioral symptoms exhibited by ASD children can be replicated.Most ASD animal model studies to date have employed transgenic mice. However, these animals often fail toreplicate all of the core ASD-like behaviors. The monogamous, biparental, and highly communicative Californiamouse (Peromyscus californicus) provides a complementary animal model for ASD research. We havepreviously demonstrated that neurobehavioral programming in California mice is especially vulnerable to BPA.Developmentally exposed males demonstrate compromised socio-sexual behaviors, and their female siblingsexhibit heightened anxiety, reminiscent of children with ASD. Both males and females developmentallyexposed to BPA go on to become poor parents as adults.We will test the hypothesis that early exposure to BPA and genistein (G), a phytoestrogen present insoy products- including baby formulas, results in ASD-like behavioral disorders in California mice. Thefirst goal will be to ascertain whether early exposure to BPA, G, and the combination of the two EDCs results inbehavioral deficits observed in ASD patients. The second goal will be to determine whether males and femalesexposed to these chemicals show gene expression/DNA methylation/miRNA (miR) changes in the brain sub-regions (amygdala, hypothalamus and hippocampus) governing these traits that may underlie the disruptedbehavioral phenotypes.Specific Aims are to: 1) Test whether developmental exposure of male and female F1 California mice to BPA,G, and BPA + G affects behavioral domains disrupted in ASD children, such as social-sexual-communicative,cognitive, anxiety/neuro-affective, and repetitive behaviors. 2) Test whether these individual and combinedEDCs affect global transcriptomic profiles in the amygdala, hippocampus and hypothalamus in F1 males andfemales that may underpin the EDC-induced behavioral disruptions. 3) Determine whether these treatmentsinduce DNA methylation and miR changes in the amygdala, hippocampus and hypothalamus in both F1 sexesand perform a comprehensive correlation analysis to link the various bio-molecular and behavioraldisturbances. Data will likely provide novel candidate biomarkers that can be used to diagnose and in potentialpreventative/remediation strategies in children at-risk for ASD due to early exposure to these EDCs.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
