# Does exposure to mitochondrial toxicants during germ cell development result in lifelong alterations in mitochondrial function mediated by epigenetic changes?

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $314,741

## Abstract

Growing evidence suggests that the toxic effects of certain chemicals on mitochondrial function can be highly
persistent. This is critical because mitochondrial function influences organismal phenotypes related to chronic
diseases such as metabolic diseases, cancers, neurodegenerative diseases, and reproductive disorders.
Therefore, exposures affecting mitochondria could contribute to these conditions. The likelihood of persistent
effects may be especially great for exposures of germ cells and gametes, because mitochondria undergo
biogenesis and major functional changes during germline proliferation and gamete production. Furthermore,
epigenetic patterns that can have long-term effects on cellular function are reprogrammed in the same time
frame. We will test the hypothesis that pollutant exposures targeting mitochondria in germ cells result
in persistent epigenetic changes that escape embryonic reprogramming and alter regulation of
pathways governing mitochondrial metabolism in offspring. We will test six important mitochondrial
toxicants: arsenic, rotenone, methyl mercury, pyraclostrobin, chlorfenapyr, and the organophosphate flame
retardant triphenyl phosphate. We will also test whether dietary restriction, which improves mitochondrial
function, and caloric overload, which has the opposite effect, will alter these outcomes. If so, this would both
reinforce our mechanistic understanding of the toxic effects of these chemicals, and provide a possible
therapeutic approach. This work will be carried out in the nematode Caenorhabditis elegans to take advantage
of very well-developed mitochondrial and epigenetic genetic tools, a rapid lifespan, and, most critically, the
availability of genetic and other tools that will allow us to mechanistically test the causality of observed
epigenetic and transcriptomic changes. Ultimately, this knowledge will improve our ability to reduce the
deleterious mitochondrial impacts of preconception exposures both by prevention (i.e., reduced exposures)
and treatment (i.e., pharmacological and lifestyle interventions to alter mitochondrial function).

## Key facts

- **NIH application ID:** 9985131
- **Project number:** 5R01ES028218-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Joel Newman Meyer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $314,741
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985131

## Citation

> US National Institutes of Health, RePORTER application 9985131, Does exposure to mitochondrial toxicants during germ cell development result in lifelong alterations in mitochondrial function mediated by epigenetic changes? (5R01ES028218-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9985131. Licensed CC0.

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