As wildfires become more frequent and intense, understanding their health risks is more important than ever. That’s why this month, I am excited to share excerpts of my recent conversation with Colette Miller, Ph.D., a principal investigator at the U.S. Environmental Protection Agency (EPA). Among her other efforts, Dr. Miller studies how exposure to wildfire smoke can affect male reproductive health and influence disease outcomes in offspring. Her work is relevant to the general public and to U.S. firefighters, more than 90% of whom are male.

At this this year’s meeting of the Society of Toxicology, Dr. Miller chaired a major session titled “It Takes Two! Paternal Exposures and Their Impact on Offspring Health.” During her presentation, she emphasized an important point. Namely, when it comes to understanding how exposures can affect development, the father’s side of the equation is too often overlooked.

In her lab, Dr. Miller simulates exposure to eucalyptus smoke, a common component of Southern California wildfires. She has discovered that male rats exposed to eucalyptus smoke for just two weeks experienced reduced sperm motility and changes in the contents of their semen — key indicators of diminished reproductive health. These findings are crucial because they suggest that even short-term exposure to wildfire smoke can have lasting negative effects.

Recently, I caught up with Dr. Miller to learn more about how those changes in male reproductive health can influence later generations. We discussed the need for further research to understand the biological mechanisms behind these effects and to develop strategies to mitigate risks associated with exposures in firefighters and other at-risk populations, such as the elderly and people with asthma. We also discussed the chemical components of different types of wildfires, and how environmental factors can influence the complexity and severity of exposure. I also asked Dr. Miller about what inspired her to pursue a scientific career.

Complex chemistry

Rick Woychik: What is in wildfire smoke, and why is it such a difficult exposure to study?

Colette Miller: I focus on wildland fires and look specifically at biomass burning, which means the burning of vegetation, trees, and other organic matter. There is a big difference between that type of fuel and what scientists call the wildland-urban interface, or WUI. This is where a wildfire moves into populated areas, and it involves biomass but also things like cars and houses, which can significantly impact the chemistry and complexity of the resulting pollution.

When we think about smoke exposure, and any sort of fire-emission exposure, we are dealing with particulate matter. With wildland fires and WUI fires, you also have volatile organic compounds and semi-volatile organic compounds. And how they interact depends on factors such as temperature, humidity, and sunlight. So, these are complex chemistries that interact at the site of the fire as well as when it ages and disperses across time and space.

When firefighters or other people close to a wildfire are exposed to smoke, it is a very different type of exposure than what is experienced by those of us, say, 10 or 20 miles away from the fire line, which is in turn different from what will eventually show up on the other side of the country. When there were wildfires in Canada last year, we saw effects here in North Carolina, but that was a very different mixture of emissions than what individuals closer to the fire experienced. This is a difficult area of science, and there are a lot of chemists trying to understand how the environment and things like photochemical aging can influence exposures and how humans respond to them.

Real-world exposure scenarios

RW: Can you describe some of your recent work on wildfire exposures?

CM: Sure. As I mentioned earlier, I focus on wildland fires. My team uses a rodent model to simulate short-term, episodic exposure to eucalyptus smoke, which is often identified in Southern California wildfires. We focus on episodic exposures and real-world smoke concentrations in an effort to mimic what many firefighters might experience on the job, and to better understand biological mechanisms behind effects in the general population.

In one of our recent studies, adult male rats were exposed to eucalyptus smoke for two weeks. We found that this exposure was enough to impair sperm motility, meaning the sperm's ability to move efficiently was diminished. Although the rats could still breed, the mature sperm collected from the cauda epididymis showed changes in certain non-coding RNA populations. These non-coding RNAs play essential roles in regulating gene expression during the early stages of embryonic development.

Generational effects

RW: That is fascinating. What did you find in terms of the health effects in offspring?

CM: We hypothesized that these alterations in sperm RNA could lead to developmental abnormalities in offspring. So, we have investigated various health aspects of the offspring, including cardiometabolic, immune, and reproductive health. So far, our findings indicate that paternal smoke exposure can indeed influence health outcomes of the next generation.

One notable finding is that female offspring from smoke-exposed fathers showed delayed pubertal timing and signs of endocrine disruption, evidenced by altered levels of hormones like estradiol and prolactin. Additionally, these offspring exhibited increased sensitivity to metabolic changes caused by high-fat diet [HFD], such as altered LDL/HDL cholesterol ratios and increased circulating inflammatory cytokines. These changes suggest that the offspring have a higher risk of developing metabolic and inflammatory conditions.

In addition, we examined the effects of smoke exposure on male offspring. The offspring from smoke-exposed fathers showed decreased levels of reproductive hormones like testosterone and luteinizing hormone, indicating potential reproductive health issues.

Key biological mechanisms

RW: So, when this smoke is breathed in, what's actually happening in the body? Beyond respiratory effects, can you speak to cardiovascular outcomes and cancer risk?

CM: There are two main hypotheses regarding how air pollutants affect cardiovascular outcomes. One is that damage markers in the lung, such as microRNAs and cytokines, could be getting out of the lung and affecting distant tissues. But what I think is more convincing in terms of severe cardiovascular events are links between air pollution exposure and the fight-or-flight response. Such exposure can induce an activation of the hypothalamic pituitary adrenal axis. And you see a strong increase in glucocorticoids, which are stress hormones, following exposure.

When the fight-or-flight response is activated, we see an increase in heart rate, and every time the heart has to work a little bit harder, there’s higher risk of atrial fibrillation. So, not just the lung but also the heart can be affected, and in fact the entire body. Numerous biological pathways get triggered, and when that happens in vulnerable populations, we can see significant negative health effects and hospitalizations, unfortunately.

When we look at wildland firefighters, we see fairly high rates of cancer, particularly lung cancer. But beyond the lung, the next most common form of cancer in this occupation is testicular cancer. I believe there's something related to the cumulative exposure that these firefighters are experiencing — not just the particulate matter but also the volatiles and semi-volatiles — that is getting to distant tissues and paving the way for cancer.

Intervention research needed

RW: Any final thoughts for Environmental Factor readers?

CM: I’d like to see high-quality clinical studies looking at potential health interventions, including ones related to nutrition and supplements. An issue with dietary supplements is that they are promising in cell-based and animal models, but when translated to humans, they have not panned out well, with some studies showing mixed effects, and others with negative findings.

My background is in nutrition, and my mind immediately goes to importance of whole foods and improving dietary quality, rather than thinking that a quick fix in the form of supplementation will help the majority of people mitigate their exposure to wildfire smoke or other forms of air pollution. Nevertheless, more research related to mitigation is needed, and I look forward to seeing more rigorous studies in this area moving forward.