PCBs in Utero Impair Hearing Health Later in Life

Music, mice, and microscopic imaging work together to reveal new information on the effects of environmental pollutants on hearing loss.
Early exposure to an environmental toxin known as polychlorinated biphenyls, or PCBs, made it more difficult for mice to recover from sound-related trauma received later in life, according to researchers at the Beckman Institute for Advanced Science and Technology.

Their study was published in the Journal of Neuroscience.

PCBs are hazardous chemicals that were previously found in industrial and consumer items. Despite the fact that they were prohibited in the United States in 1979 and haven’t been used in industry for decades, their highly stable chemical structure makes them tough to remove from the environment. To this day, exposure is most common through the ingestion of infected fish. PCBs, in particular, can be detrimental to a developing fetus.

The most sensitive period in pregnancy for these types of developmental exposures is typically early in the pregnancy, in the first trimester,” said Dr. Daniel Llano, an associate professor in the Department of Molecular and Integrative Physiology at the University of Illinois Urbana-Champaign and the corresponding author on the paper. “But PCBs as chemical entities are very permeant to all sorts of membranes. They can cross the placenta and they can get into the brain. That makes them particularly dangerous throughout all phases of pregnancy.”

Susan Schantz, a professor emerita in the Department of Comparative Biosciences who was exploring the effects of PCBs on the developing auditory system, established the framework for the research several years ago. She discovered that rats given PCBs had convulsions in reaction to particular levels of sound.

This led to a partnership between Schantz, Llano, and the paper’s lead author, Baher Ibrahim, a research scientist in the Department of Molecular and Integrative Physiology. Although the researchers had known for years that PCBs had an effect on hearing, they sought to know how.

The researchers suspected that if a person exposed to PCBs in utero suffered acoustic trauma later in life (for example, from a job that requires a lot of noise or even from a recreational activity like going to a rock concert), their hearing might not recover as well as it should.

Instead of focusing on the auditory cortex, the researchers turned their attention to the inferior colliculus, a lower brain region. They discovered harm caused by the combination of PCBs and noise.

They used a method known as multiphoton imaging to study individual neurons in the brains of the animals.

“This is a one-of-a-kind microscope, and we are one of very few labs in the world doing this particular kind of imaging in this brain region,” Llano said. “People have shown in the past that if you expose a mouse to loud sound, over time, the neurons in the inferior colliculus become hyper-responsive. But when combining the two toxic exposures, PCBs and noise, and using our imaging technique, that hyperexcitability went away.”

The researchers also noticed that the neurons become hypo-excitable, which was a novel discovery.

The researchers employed chemical analyses to better understand the mechanisms underlying these alterations. Their research focused on oxidative stress, a normal biological activity that automatically releases oxygen radicals—or highly reactive chemicals—when cells are unwell or exposed to pollutants. An inherent system within the body eliminates oxygen radicals.

Mice with higher levels of the intrinsic protective mechanism had less damage to the inferior colliculus, implying that PCBs and noise may induce an excess of oxidative stress in the inferior colliculus, inhibiting the auditory system’s ability to recover from acoustic trauma.

“On its own, PCB exposure in utero may cause only a moderate degree of hearing loss,” Llano said. “But that PCB exposure creates a particular vulnerability to later hearing loss. And so someone who is exposed to PCBs during development and has a significant occupational or recreational exposure to sound later in life may suffer greater-than-expected consequences when it comes to hearing.”

In contrast to typical toxicological studies that look at a single exposure, the Beckman research team took into account two exposures—PCBs and noise—experienced in distinct instances over the course of a lifetime.

“What we found were effects that would not have been predictable based on the separate impacts of the individual exposures,” Llano said. “You can’t necessarily predict the consequence of combined exposure to two environmental factors by adding up the effects of either one by itself. I think that’s one of the more interesting things about this study, and hopefully it can be used as a model for future toxicology studies.”

The research team will continue to look into the links between PCB exposure, noise exposure, and hearing loss. While oxidative stress appears to be an important mediator of the effect, researchers have yet to test oxygen radicals in tissues to validate this.

“Dr. Llano and I have now co-mentored a graduate student and three postdocs who have carried this research forward,” Schantz said. “We are about to embark on the next stage of our collaboration, co-mentoring a fourth postdoc who will study the microvasculature of key brain regions after PCB and noise exposure.”

These research questions will be pursued in the same location where the project began: the Beckman Institute.

“This is the kind of study that could only occur at Beckman,” Llano said. “Dr. Schantz and I are in entirely different departments. Our home departments are in completely different locations on campus, but our Beckman offices are 10 feet apart. Because of that, it’s made it very easy for us to collaborate. I think this is the kind of study that would be almost impossible to do in a different environment where we didn’t have easy access to each other’s ideas and the various interactions that exist here.”

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