# Endocrine Disrupting Chemicals, Epigenetic Alterations, and Autism-Like Behaviors in the Highly Social California Mouse Model

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $378,215

## Abstract

Project Summary
Increasing numbers of children are being diagnosed with autism spectrum disorders (ASD and related
neurobehavioral disorders. Based on the rising incidence that is not explained by genetics alone, it has been
postulated 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), including
bisphenol 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 core
behavioral symptoms exhibited by ASD children can be replicated.
Most ASD animal model studies to date have employed transgenic mice. However, these animals often fail to
replicate all of the core ASD-like behaviors. The monogamous, biparental, and highly communicative California
mouse (Peromyscus californicus) provides a complementary animal model for ASD research. We have
previously demonstrated that neurobehavioral programming in California mice is especially vulnerable to BPA.
Developmentally exposed males demonstrate compromised socio-sexual behaviors, and their female siblings
exhibit heightened anxiety, reminiscent of children with ASD. Both males and females developmentally
exposed 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 in
soy products- including baby formulas, results in ASD-like behavioral disorders in California mice. The
first goal will be to ascertain whether early exposure to BPA, G, and the combination of the two EDCs results in
behavioral deficits observed in ASD patients. The second goal will be to determine whether males and females
exposed 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 disrupted
behavioral 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 combined
EDCs affect global transcriptomic profiles in the amygdala, hippocampus and hypothalamus in F1 males and
females that may underpin the EDC-induced behavioral disruptions. 3) Determine whether these treatments
induce DNA methylation and miR changes in the amygdala, hippocampus and hypothalamus in both F1 sexes
and perform a comprehensive correlation analysis to link the various bio-molecular and behavioral
disturbances. Data will likely provide novel candidate biomarkers that can be used to diagnose and in potential
preventative/remediation strategies in children at-risk for ASD due to early exposure to these EDCs.

## Key facts

- **NIH application ID:** 10016304
- **Project number:** 5R01ES025547-05
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** R. MICHAEL ROBERTS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,215
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016304

## Citation

> US National Institutes of Health, RePORTER application 10016304, Endocrine Disrupting Chemicals, Epigenetic Alterations, and Autism-Like Behaviors in the Highly Social California Mouse Model (5R01ES025547-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10016304. Licensed CC0.

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