At the end of June 2024, the five-year international project OBERON was completed. The project aimed to better understand and identify environmental substances that can disrupt hormonal regulation in the human body. The project was funded by the European Union’s Horizon 2020 framework grant program, and the RECETOX center was involved at several levels.
Endocrine-disrupting chemicals (EDCs) are substances that disrupt hormonal regulation in the body. This disruption can lead to various diseases or adverse health effects, ranging from developmental and reproductive disorders to metabolic disorders. EDCs currently represent one of the most critical risks to public health. To regulate the use of these substances within the European Union, it is necessary to develop new and effective methods for testing their harmful effects.
The OBERON project aimed to develop an integrated testing strategy to detect the impact of EDCs on metabolic diseases such as obesity, type II diabetes, or liver steatosis. The project combined knowledge from epidemiological studies, advanced in silico computational models predicting the biological activity of substances from their chemical structure and properties, with experimental methods using in vitro tissue cultures and early developmental stages of fish in vivo. This approach was supported by systems biology tools and so-called omics technologies, which mapped changes in gene expression and metabolic pathways due to the action of endocrine disruptors (EDCs).
EDCs that are most commonly found in the environment and human populations were thoroughly examined. The project’s goal was to demonstrate causality between their effects and the impacts on human health, to describe in detail the involved molecular and biochemical processes, and to develop tools that could reliably recognize the harmful effects of substances disrupting human metabolism.
“The project was primarily focused on the question of whether these substances can disrupt human metabolism and understanding the mechanisms involved. Based on this knowledge, the goal was to propose and develop tools that would allow us to timely recognize dangerous substances with such effects and implement regulatory measures before they start to be produced and used,” explains Associate Professor Pavel Babica, the project researcher from Masaryk University.
RECETOX was involved in OBERON with the CELSPAC Young Adults population cohort. The team led by Professor Klánová monitored EDCs levels in the population, their frequencies, and possible associations with metabolic diseases. Additionally, the RECETOX team studied the impact of EDCs on liver and adipose tissue. Associate Professor Pavel Babica’s team primarily investigated the ability of EDCs to cause liver steatosis, a disease estimated to affect up to a quarter of the world’s population. They optimized in vitro tests with human liver cells to evaluate the potential of EDCs and other chemicals to induce liver steatosis. Professor Julie Dobrovolná’s group experimentally examined the ability of EDCs to impact the differentiation and characteristics of human adipose cells. RECETOX scientists were also involved in developing new bioinformatics tools to map the mechanisms responsible for the harmful effects of EDCs.
A key aspect of the project was linking the obtained data across the involved institutions to create comprehensive knowledge of EDCs. Based on this knowledge, to propose a strategy for testing their effects on metabolism.
"The findings from the project helped to elucidate the mechanism of action of metabolic disruptors and identify additional biomarkers for more effective and timely detection of substances with such effects. The outputs also include newly developed bioinformatics tools, computational models, and experimental methodologies. These tools will not only serve further scientific research,but are now being evaluated at the European level for use in the process of chemical registration and authorization, as well as in other sectors of chemical regulation,” explains Pavel Babica.
Publications:
Endocrine disruption of adipose physiology: Screening in SGBS cells
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