# The Epigenetics Crossroads of Environmental Exposures and Early-Life Adversity

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $189,363

## Abstract

ABSTRACT
Our capacity for health and disease is intimately tied with the environment and the experiences to which we are
exposed. Life experiences, then, can yield lasting consequences on development, behavior, and health. Those
occurring during the sensitive period early in life can be especially potent. Early life adversity (ELA) is highly and
universally prevalent, and accounts for increased mortality, as well as increased rates of mental and physical
pathophysiology. This is manifested in the incidence of mental health disorders and chronic medical conditions
well into adulthood, as well as cardiovascular disease, inflammation, obesity, and cancer. Studies suggest that
60.9% of adults reported to have experienced a minimum of one type of adverse childhood exposures (ACE),
and 15.9% experienced multiple ACEs. This recent statistic underscores the sheer prevalence and far-reaching
consequences of ELA on human health and behavior, as well as emphasizing the importance of studies that
consider multiple contemporaneous ACEs.
The association of environmental exposures (including air pollution and traumatic ELA) and epigenomic changes
has been well-recognized. However, in order to inform interventions that address public health issues effectively,
the tantamount question regarding the pathophysiological bases of ACEs – how they “get under the skin” via
epigenome modification, and how and which of these epigenomic changes are causally or functionally relevant
to the disease phenotypes observed – remains poorly understood. In this proposal, we will identify epigenetic
and genetic events with robust phenotypic consequences occurring in a mouse model of ACE. We will use a
unique model at UC Davis in which mice are exposed to traffic-related air pollution (TRAP) during development,
representing an environmental factor known to be associated with increased risk of neurodevelopmental
disorders, including cognitive impairment, psychomotor deficits, and hyperactivity. As a contemporaneous ACE,
we will apply the limited bedding and nesting (LBN) paradigm of fractured caregiving, associated with several
similar phenotypic outcomes. We hypothesize that the two ACEs will have additive or synergistic effects on
molecular and behavioral outcomes. Complementary to these studies, we will investigate the hypothesis that
changes in epigenetic information are an important physical component of how chronic adverse childhood
exposures manifests consequences later in life. This project builds upon an interest in studying glucocorticoid
receptor (GR) expression and regulation in the dorsal hippocampus – whether specific gene expression changes
induce specific structural and functional changes has not yet been ascertained. We expect to identify distinct
and functionally noteworthy epigenetic “signatures” related to these phenotypic characteristics, based on related
studies. The long-term goal of this study is to identify and prioritize epigenetic events and robust phenotype...

## Key facts

- **NIH application ID:** 10490289
- **Project number:** 5R21ES033460-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Keith Bein
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $189,363
- **Award type:** 5
- **Project period:** 2021-09-17 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490289

## Citation

> US National Institutes of Health, RePORTER application 10490289, The Epigenetics Crossroads of Environmental Exposures and Early-Life Adversity (5R21ES033460-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10490289. Licensed CC0.

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