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

Award Number: R01ES025547
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2016
PERIOD OF PERFORMANCE END DATE: 08/31/2022

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = -$3,276 )
2023	2020	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Environmental Health	000	5	4/27/2023	NON-COMPETING CONTINUATION	-$3,276
														Subtotal = -$3,276

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Environmental Health	000	5	2/24/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $378,215 )
2020	2020	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Environmental Health	000	5	8/10/2020	NON-COMPETING CONTINUATION	$378,215
														Subtotal = $378,215

Issue Date FY: 2019 ( Subtotal = $378,485 )
2019	2019	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Environmental Health	000	4	9/11/2019	NON-COMPETING CONTINUATION	$378,485
														Subtotal = $378,485

Issue Date FY: 2018 ( Subtotal = $374,647 )
2018	2018	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Environmental Health	000	3	8/30/2018	NON-COMPETING CONTINUATION	$374,647
														Subtotal = $374,647

Issue Date FY: 2017 ( Subtotal = $386,912 )
2017	2017	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Environmental Health	000	1	4/30/2017	SUPPLEMENT FOR EXPANSION	$8,618
2017	2017	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Environmental Health	001	2	8/29/2017	NON-COMPETING CONTINUATION	$378,294
														Subtotal = $386,912

Issue Date FY: 2016 ( Subtotal = $375,874 )
2016	2016	CURATORS OF THE UNIVERSITY OF MISSOURI	5100 Rockhill Road	Kansas City	MO	64110	JACKSON	USA	Environmental Health	000	1	8/26/2016	NEW	$375,874
														Subtotal = $375,874

Grand Total All Awards = $1,890,857

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

Award Number: R01ES025547

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2016

PERIOD OF PERFORMANCE END DATE: 08/31/2022

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