# Mechanisms of memory of environmental exposure: determining the role of histone modifications in regulating transgenerational behavior effects caused by environmental chemical exposure.

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $49,556

## Abstract

Project Summary of Parent Award
 The long-term goal of this project is to identify the mechanisms of germ cell sensitivity to
environmental exposures and their long-lasting, transgenerational effects. Germ cells are the
bridge between generations and their integrity is paramount to the health and viability of all
organisms. As such, the dysregulation of germ cells development and function significantly
contributes to infertility and is also the leading cause of birth defects and infant deaths in the
United States. While the intricate steps of germ cell development have long been hypothesized
to provide unique windows of sensitivity to environmental insults, little is known of the effect of
chemical exposure on the epigenome of germ cells and of the mechanisms of inheritance of
these effects.
 This gap is particularly significant as embryonic germ cells undergo an extensive
remodeling of their chromatin which includes genome-wide demethylation and the
establishment of a complex pattern of histone modifications. The failure to properly regulate
these histone marks leads to spurious repetitive element expression, germ cell death and
infertility. Furthermore, preliminary evidence gathered in the powerful genetic model system C.
elegans indicates that exposure to chemicals such as Bisphenol A leads to a heritable,
transgenerational defect in chromatin silencing of repetitive DNA.
Here, we propose to leverage two complementary germ cell models, the nematode C. elegans
and in vitro generated mouse germ cells, to elucidate the molecular mechanisms underlying the
epigenetic effects of Bisphenol A. We will achieve this goal by (1) Characterizing the sensitivity
of early mammalian germ cells to BPA exposure and establish the long term, transgenerational
outcome on reproduction in C. elegans; (2) Providing a comprehensive and detailed
examination of epimutations caused by BPA and of their transcriptional consequence; and
finally by (3) Identifying the genetic requirements for both germ cell sensitivity to direct exposure
as well as for the transmission of epigenetic effects across generations.
 We expect this research to provide a much-needed examination of the pathways
implicated in the sensitivity of early germ cells to environmental insults and at the root of
infertility.

## Key facts

- **NIH application ID:** 9943628
- **Project number:** 3R01ES027487-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Patrick Allard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $49,556
- **Award type:** 3
- **Project period:** 2017-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9943628

## Citation

> US National Institutes of Health, RePORTER application 9943628, Mechanisms of memory of environmental exposure: determining the role of histone modifications in regulating transgenerational behavior effects caused by environmental chemical exposure. (3R01ES027487-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9943628. Licensed CC0.

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