# Mechanisms of environmental epigenetic disruption and memory of exposure in germ cells

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $408,052

## Abstract

PROJECT SUMMARY/ABSTRACT
 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:** 10112905
- **Project number:** 5R01ES027487-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Patrick Allard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $408,052
- **Award type:** 5
- **Project period:** 2017-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112905

## Citation

> US National Institutes of Health, RePORTER application 10112905, Mechanisms of environmental epigenetic disruption and memory of exposure in germ cells (5R01ES027487-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10112905. Licensed CC0.

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