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Growing research on per- and polyfluoroalkyl substances (PFAS) in recent decades has brought to light an unfortunate reality: these “forever chemicals” are ubiquitous in our environment, and they can be toxic to our health.
The umbrella term PFAS refers to a large family of synthetic chemicals that have been used in the manufacturing of consumer goods since the 1950s. The presence of an incredibly strong carbon and fluorine bond equips PFAS molecules with unique properties – once considered “beneficial” – including resistance to heat, oil and stains. This man-made bond is now known to underpin the chemicals’ unwavering persistence in the environment.
Animal and human studies have linked PFAS exposure to various health conditions, including different forms of cancer, metabolic disorders, obesity, disrupted brain development and cardiovascular disease, among others. In response, global organizations are working to develop and implement PFAS regulations and restrictions – but there are many challenges.
PFAS molecules have been detected almost everywhere – in the food we consume, in drinking water, clothes and even human blood. And while there are thousands of known PFAS, there are even more out there yet to be identified. This contributes to a third issue: while PFAS have been associated with some human diseases, there’s no definitive answer as to how these molecules might lead to the development of, or directly cause, such diseases.
Dr. Jaclyn (Jackie) Goodrich’s work at the University of Michigan School of Public Health aims to identify environmental factors that could influence disease susceptibility in vulnerable populations. Her ongoing research contributes to a growing body of evidence suggesting that PFAS exposure can impact the epigenome.
Epigenetics concerns changes in gene regulation that do not result from a direct change to nuclear DNA. There are many different types of epigenetic modifications that can occur in response to internal or external stimuli. DNA methylation, where a methyl (CH3) group is transferred to a DNA molecule, impacting how proteins responsible for gene activation can bind to it, is the most commonly studied. Epigenetic changes might have negative consequences on a cell or tissue’s biology. For example, DNA methylation can play a critical role in the initiation and progression of cancer.
In this interview with Technology Networks, Goodrich provides a helpful overview of what we know about PFAS exposure and epigenetic modifications. She also puts forth suggestions on how to address the unknowns in this research space.
Molly Coddington (MC):
Senior Writer and Newsroom Team Lead
Technology Networks
Molly Coddington is a Senior Writer and Newsroom Team Lead at Technology Networks. She holds a first-class honors degree in neuroscience. In 2021 Molly was shortlisted for the Women in Journalism Georgina Henry Award.
Can you introduce our readers to epigenetics, and how this research field can help to advance our understanding of environmental effects on human health?
Jackie Goodrich (JG):
Research Assistant Professor
Dr. Jaclyn Goodrich is a research assistant professor in the Department of Environmental Health Sciences at the University of Michigan School of Public Health.
We encounter exposure to chemicals on a daily basis through consumer products, contaminated food and water, polluted environments and more. Some of these exposures have a negative impact on health, including increased risk for cancers, metabolic disorders and other health issues. There are many ways these chemicals can exert effects in the body.
At the cellular level, some exposures can affect how genes are turned on and off by impacting the set of marks on top of DNA. This regulatory network is called the epigenome.
Senior Writer and Newsroom Team Lead
Technology Networks
Molly Coddington is a Senior Writer and Newsroom Team Lead at Technology Networks. She holds a first-class honors degree in neuroscience. In 2021 Molly was shortlisted for the Women in Journalism Georgina Henry Award.
What do we know – and what don’t we know – about how PFAS impact the human body at different stages in life?
JG:
Research Assistant Professor
Dr. Jaclyn Goodrich is a research assistant professor in the Department of Environmental Health Sciences at the University of Michigan School of Public Health.
PFAS are one set of toxic chemicals we encounter. Our knowledge of the adverse health impact from PFAS exposure is growing. We know that PFAS increases risk for certain cancers, high cholesterol, thyroid problems and more. Children that were exposed to PFAS during gestation or in early childhood may be particularly susceptible to PFAS’ effects. PFAS has been linked to low birth weight and reduced vaccine response in children. There is also some evidence for metabolic and neurodevelopmental outcomes in children exposed to PFAS, though this evidence is more mixed.
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Senior Writer and Newsroom Team Lead
Technology Networks
Molly Coddington is a Senior Writer and Newsroom Team Lead at Technology Networks. She holds a first-class honors degree in neuroscience. In 2021 Molly was shortlisted for the Women in Journalism Georgina Henry Award.
Can you explain why epigenetic perturbations could be a mechanism by which PFAS cause adverse health effects? What evidence (so far) supports this notion, or perhaps disputes it?
JG:
Research Assistant Professor
Dr. Jaclyn Goodrich is a research assistant professor in the Department of Environmental Health Sciences at the University of Michigan School of Public Health.
There have been dozens of studies in animal models and human cohorts that demonstrate links between PFAS exposures and altered DNA methylation (one major form of epigenetic regulation) at various genes.
These studies, including my own in human populations, provide compelling evidence that PFAS can impact epigenetic regulation. However, most studies have measured DNA methylation and not other types of epigenetic regulation (i.e., non-coding RNA, histone modifications or chromatin structure).
Goodrich highlights two review papers, published in
2021 and
2023, which summarize existing evidence on PFAS and epigenetic changes.
We also need to know whether PFAS impacts these other layers of regulation.
Senior Writer and Newsroom Team Lead
Technology Networks
Molly Coddington is a Senior Writer and Newsroom Team Lead at Technology Networks. She holds a first-class honors degree in neuroscience. In 2021 Molly was shortlisted for the Women in Journalism Georgina Henry Award.
In March 2023, you published the first report of widespread 5-hmC alterations after prenatal PFAS exposure. Can you share how the research field has progressed since then?
JG:
Research Assistant Professor
Dr. Jaclyn Goodrich is a research assistant professor in the Department of Environmental Health Sciences at the University of Michigan School of Public Health.
Ours was the first human study to focus on PFAS and DNA hydroxymethylation specifically. The laboratory methods typically used do not distinguish between hydroxymethylation and standard DNA methylation, yet we know these two modifications have their own distinct influences on gene regulation.
We found thousands of genetic loci where cord blood hydroxymethylation levels were linked to higher PFAS concentrations during pregnancy. Hydroxymethylation and PFAS exposure have not been examined in another cohort since then, that I am aware of, but this will be important try to replicate in other human populations and animal models of early life exposure.
Senior Writer and Newsroom Team Lead
Technology Networks
Molly Coddington is a Senior Writer and Newsroom Team Lead at Technology Networks. She holds a first-class honors degree in neuroscience. In 2021 Molly was shortlisted for the Women in Journalism Georgina Henry Award.
Can you describe the key challenges associated with studying the mechanisms by which PFAS exert their effects on human health, in the context of epigenetics?
JG:
Research Assistant Professor
Dr. Jaclyn Goodrich is a research assistant professor in the Department of Environmental Health Sciences at the University of Michigan School of Public Health.
Key challenges include our limited ability – in most human studies – to profile epigenetic marks beyond DNA methylation in blood. The epigenome is tissue-specific, and PFAS may impact the epigenome of key organs like the liver, brain and adipose tissue differently than what we can see in blood.
There are also thousands of known PFAS, but research tends to focus on the ~dozen that we can measure well. Efforts are underway in the environmental health community to better understand toxicity and risks from other types of PFAS.
Senior Writer and Newsroom Team Lead
Technology Networks
Molly Coddington is a Senior Writer and Newsroom Team Lead at Technology Networks. She holds a first-class honors degree in neuroscience. In 2021 Molly was shortlisted for the Women in Journalism Georgina Henry Award.
What do you view as big, “unresolved” questions in this line of work? How would you hope to address them?
JG:
Research Assistant Professor
Dr. Jaclyn Goodrich is a research assistant professor in the Department of Environmental Health Sciences at the University of Michigan School of Public Health.
We do not yet know if the epigenetic alterations we observe directly cause downstream health effects in PFAS-exposed individuals. We also do not know if the epigenetic changes we observed in blood also occur in other key tissues. We can start to resolve these questions by using animal models of exposure.
Dr. Jackie Goodrich was speaking to Molly Coddington, Senior Science Writer and News Team Lead at Technology Networks.
