Pregnancy and environmental chemical mixtures: the alarm of science
The results of the European study EDC-MixRiskpublished in the prestigious scientific journal “Science”, show that, during pregnancy, the mix of environmental chemicals to which we are continuously exposed, interfering with our endocrine system, increases the risk of neurological deficit in the unborn childespecially a speech delay. Responding to a need long highlighted by various regulatory agencies, this work therefore lays the scientific foundations for a radical revision of national and international risk assessment policies, hitherto based on the examination of single substances and not their mixtures. The study, funded by the European Union, was conducted in collaboration between universities and centers in various countries.
The threat comes from the pollution of air, water and food
Every year, as part of the authorization processes for the production and marketing of a wide range of products, starting with plastic derivatives, up to cosmetics and pesticides, a huge number of chemical compounds that enter the human body through water, food and air. We know that although exposure levels for individual chemicals are often below the established limit, exposure to the same chemicals in complex mixtures it can have a negative impact on human health. However, current risk assessments, and the limits set accordingly, have so far been based on the examination of individual chemicals. It was therefore essential to verify the possibility of an alternative risk assessment strategy, which would allow us to test the mixes of substances to which we are actually exposed in an epidemiological and experimental context. The EDC-MixRisk project has given an answer to this need.
How the scientific research took place
The study was conducted in three phases: with the SELMA study – which followed about 2,000 women from the beginning of pregnancy to the school age of the children – it was identified a mix of chemicals in the blood and urine of pregnant women associated with delayed speech development in babies by the age of 30 months. The mix included a number of phthalates, bisphenol A (BPA) and perfluorinated compounds (PFAS). Subsequently, very advanced experimental studies uncovered the molecular targets through which critical levels of this mix altered the regulation of endocrine circuits and genes involved in autism and intellectual disability. Finally, the results of the experimental studies were used to develop specific risk assessment methods for the substance mix. Thanks to these new experimentally defined risk thresholds, it emerged that up to 54% of pregnant women had been exposed to an increased risk of language delay in the unborn.
The comment of the researchers
“This study is a milestone for the protection of public health and makes it impossible to postpone a legislative adjustment that reflects the new risk framework for environmental toxic substances, highlighted for the first time in a systematic way by our data. Its uniqueness also lies in having demonstrated the feasibility and effectiveness of the synergy between population and laboratory studies: a new method that can be applied to other public health issues. In Italy we took care of the experimental phase in the laboratories of the European Institute of Oncology, which will now continue in the Neurogenomics Center of the Human Technopole. Human brain organoids (sophisticated in vitro cultures that reproduce salient aspects of human brain development) have offered, again for the first time, the opportunity to directly probe the molecular effects of the chemical mix on human brain tissue. , in phases corresponding to those observed during pregnancy. We found that, even at low concentrations, the mix directly interferes both with some genes involved in brain development and with others linked to autism (characterized by the language disorder) “he explains Giuseppe TestaPrincipal Investigator of EDC-MixRisk responsible for human experimental modeling, professor of molecular biology at the University of Milan, director of the Neurogenomics Center at Human Technopole and group leader at the European Institute of Oncology.
Second Nicolò Caporale and Cristina Cheroni, among the first authors of the study, “With the work of our laboratory we have integrated the epidemiological evidence relating to the mix of endocrine disruptors with the understanding of its mechanisms of action, shedding light on how it acts on the human brain and how it can create damage to its development. Thanks to innovative experimental models, we exposed in the laboratory human neuronal progenitors and brain organoids at different concentrations of the mix and characterized their impact both at the level of gene regulation with transcriptomics experiments, and at the cellular level with microscopy techniques, discovering that it was altered neuron development, and that thyroid hormone regulation was one of the main targets involved. As expected for such a complex aspect as language acquisition, it should be emphasized that exposure significantly increases the risk of neurological damage to which numerous other factors can also contribute, primarily at the level of individual genetic predisposition. Far from limiting the value of our study for policy makers, this reinforces it because the mix of toxic substances is a risk factor that can be acted upon, unlike others, with adequate legislation. We think that one of the potentials of our research is therefore to inaugurate a new toxicology in support of European environmental policy ”.
“We are proud to have contributed to this very important study by providing our advanced research structure, able to guarantee researchers the best conditions to develop basic, academic, studies in different scientific fields. There is only one science and the technologies we use for oncology also lend themselves to other areas, specifically neuroscience and wide and diverse applications “, comments Prof. Roberto OrecchiaIEO Scientific Director.
Maria Pia Abbracchio, Deputy Rector Delegate for the Coordination and Promotion of Research of the University of Milan, concludes: “It has been known for years that the developing nervous system is particularly susceptible to permanent effects and developmental delays following early exposure to substances toxic during the antenatal period. This study demonstrates that, just like drugs, low doses of a single interfering agent can synergize with other substances, inducing effects even at apparently non-toxic dosages. The study also introduces a reliable method for assessing the complexity of risk, revolutionizing the concept of minimum toxic dose for individual chemical substances and underlining the need to determine the global effect induced by the mix of interferents to which the pregnant mother can be exposed “.