New Biomarkers: Advancing Our Knowledge of Children’s Neurodevelopment and Chemical Exposures

Published January 15, 2025

Protecting children’s health is one of EPA’s top priorities. Children are often more vulnerable than adults to harmful chemical exposures due to their smaller size, developing bodies, and unique behaviors. Yet, uncertainties and challenges remain in understanding early life-stage chemical exposures and the consequences that these exposures may have later in life.

Current methods for monitoring the impact of chemical exposures on the developing brain are expensive and time-consuming. Dr. Katie O’Shaughnessy, an EPA researcher studying the effect of thyroid-disrupting chemicals on children’s neurodevelopment, approached these challenges with research support through EPA’s Pathfinder Innovation Projects (PIPs) program. The PIPs program is an annual, internal competition that provides EPA staff with time and funding to pursue highly innovative research ideas. Under her PIPs project, O’Shaughnessy and her team developed a methodology to view a real-time assessment of brain health using microRNAs (miRNAs) as a non-invasive biomarker from a small blood sample.

O’Shaughnessy and her team initially received PIP support for work on this project in 2018. During this first phase, the team successfully identified nine miRNAs that increased during gestational exposure to thyroid disrupting chemicals. Based on the success of these findings, the team received additional PIP funding the following year to continue working on the project. The purpose of this additional work was to demonstrate that the identified miRNAs come from the brain, are predictive of developmental neurotoxicity, and change in response to various thyroid disrupting chemicals.

“This project could increase EPA’s ability to quickly identify and mitigate chemical exposures that negatively affect childhood development,” O’Shaughnessy explained.

O’Shaughnessy’s research focuses on exposures to endocrine disruptors, chemicals that mimic naturally occurring hormones and disrupt thyroid function – which is crucial for brain development. Exposure can lead to altered brain structure and function, negatively impacting children’s cognitive, emotional, and social capacities.

To assess potential risks in children’s neurodevelopment, scientists often measure thyroxine (T4) levels, a hormone produced by the thyroid gland. However, there are limitations to this method. While thyroxine levels can indicate hormonal disruption and potential neurotoxicity, they do not indicate when neurological harm occurs. Additionally, the specific neurological effects in humans can be difficult to measure. O’Shaughnessy’s research suggests that disrupted thyroid levels affect brain barriers, the dynamic boundaries that separate the central nervous system from the bloodstream. The team hypothesized that brain barrier functions disturbed by abnormal thyroid function will result in traceable molecules escaping from the brain tissue and entering the bloodstream. These molecules can appear in blood samples and indicate developmental neurotoxicity caused by thyroid issues.

“Currently, most toxicology research only examines the effects of one chemical at a time. This, unfortunately, is not what people are exposed to in everyday life,” says O’Shaughnessy. In this research, she identifies a “biomarker of effect,” representing a biological change resulting from chemical exposures. Biomarkers can be used to evaluate exposure to different chemicals and their mixtures, providing a more accurate representation of what people experience in everyday life.

As described in their publication, while conducting in vivo testing, the team found reduced thyroxine levels in the offspring. miRNAs help cells to control gene expression and are widely considered to be sensitive biomarkers for disease like cancer and Alzheimer’s. In this study, the team identified two miRNAs, miR-495 and miR-543-3p, that increased in response to reduced thyroxine levels and also reflected neurodevelopmental disturbances. These results suggest that these miRNAs have the potential to serve as new biomarkers for thyroid-related developmental neurotoxicity in living organisms that can be used as a rapid and inexpensive detection method. The team’s work was featured on the cover of the March 2024 issue of Toxicological Sciences.

“These results will be of great importance to scientists and organizations that study developmental and reproductive toxicity. The biomarkers discovered can help these toxicologists decide if certain chemicals, such as new pesticides, may be detrimental to brain development,” O’Shaughnessy stated. “In the more distant future, we hope that this work could be applied to human populations.”

O’Shaughnessy and her team expanded their biomarker research from the PIPs exploration into continuing work that has been adopted into EPA’s research plans. Moving forward, they will continue their biomarker research by testing other chemical exposures, including both neutral and harmful exposures, and working towards a standardization of methods. These are necessary steps to integrate this technology into developmental and reproductive toxicity studies.

“This research shows that it is possible to identify biomarkers that rapidly readout neurological effects,” O’Shaughnessy said. “This work furthers the team’s goal to identify testing strategies to evaluate chemical toxicity more effectively.”

The continuation of this research will inform public health experts’ abilities to assess the neurodevelopmental impacts on children living in polluted areas, allowing for improved reduction of exposures that may negatively impact children’s health.