# Epigenetic and metabolic mechanisms of environmentally-induced transgenerational germline dysfunction

> **NIH AA R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2026 · $344,429

## Abstract

PROJECT SUMMARY
 The overarching goal of the research presented in this application is to dissect the genetic, epigenetic, and
metabolic programs that encode and transmit a memory of environmental exposure for several generations. In
that context, we aim to understand how environmental influences alter the reproductive program of organisms
in a transgenerational fashion and what makes the germline a particularly important and sensitive target of
exposures.
 In mammals, in utero ethanol exposure is associated with an array of well-characterized morphological,
neurobehavioral, and reproductive issues. However, there is mounting evidence in a variety of model
organisms that some adverse reproductive and neurological features are also detectable in the third generation
following exposure indicating a transgenerational effect. Alcohol also has a clear epigenetic impact and directly
contributes to the modification of the epigenome. Nevertheless, despite the fact that heritable effects of alcohol
imply an alteration of the information contained in germ cells, it is unclear how the memory of ethanol exposure
is initiated in the germline and then transmitted to future generations. Here, we combine the tractability and
conservation of the model system C. elegans with state-of-the-art epigenomic analyses, classical genetic, and
cytological approaches to shed light on the mechanisms of memory of ethanol exposure. Our preliminary data
shows that ethanol exposure causes strong transgenerational reproductive and behavioral impairments. We
also show that, in line with recent mammalian studies, ethanol causes an increase in histone acetylation.
Thus, we hypothesize that ethanol exposure causes transgenerational perturbations of germline
function by altering the germline epigenome, specifically histone acetylation. Our aims are designed to
address the molecular, metabolic and epigenetic requirements for these transgenerational impacts of ethanol.
In aim 1, we will build on our prelim

## Key facts

- **NIH application ID:** 11377002
- **Project number:** 5R01AA030160-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Patrick  Allard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AA
- **Fiscal year:** 2026
- **Award amount:** $344,429
- **Award type:** 5
- **Project period:** 2023-06-01T00:00:00 → 2028-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11377002

## Citation

> US National Institutes of Health, RePORTER application 11377002, Epigenetic and metabolic mechanisms of environmentally-induced transgenerational germline dysfunction (5R01AA030160-04). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/11377002. Licensed CC0.

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