Many of the chemicals we are exposed to in our everyday lives affect our bodies by acting in a similar way to hormones. In a combination of epidemiological and experimental studies, researchers have now examined how mixtures of such pollutants affect the brain development of unborn children. Their result: Even with exposures that are below the limit values for each individual chemical, the mixture can increase the risk of problems such as language development disorders and autism.
Pesticides, plasticizers, heavy metals: we ingest a large number of industrial chemicals every day in different ways. They reach us through the air we breathe, drinking water or our food. Some of them belong to the so-called hormone-active endocrine disruptors (EDC). Since they have similar effects to hormones, they can influence our body processes, including gene regulation, even in small amounts. There are limit values for the individual chemicals. How the combination of different EDCs affects us, however, has so far received little attention.
Mix of chemicals in the urine of pregnant women
A team led by Nicolò Caporale from the European Institute of Oncology in Milan has now investigated how the mixture of different environmental chemicals affects the brain development of unborn children. “The uniqueness of this comprehensive project is that we combined population data with experimental studies and then used this information to develop new methods for risk assessment of chemical mixtures,” says co-author Carl-Gustaf Bornehag, from Karlstad University in Sweden .
In the epidemiological part of the study, the researchers used data from a Swedish cohort study that follows mother-child pairs from pregnancy to the child’s primary school age. From a total of 1874 mothers, they identified those whose children could speak fewer than 50 words by the age of 2.5 years – a defining feature of a language development disorder. The researchers then examined blood and urine samples taken from the mothers in the tenth week of pregnancy for the content of 15 different EDCs. The chemical combinations that were more detectable in the mothers of the late language developers classified them for further investigation as a potentially harmful mix of these chemicals.
Among the chemicals the researchers found in the pregnant women’s urine were common additives in plastics such as bisphenol-A and phthalates, as well as triclosan, which is used in cosmetics and disinfectants. To find out exactly how the combination of these chemicals affects the brain, the researchers used what are known as brain organoids. These are miniature brain models grown from human stem cells. These exposed Caporale and his team to varying concentrations of the chemicals in question. Additionally, they performed similar experiments on tadpoles and zebrafish.
Many unborn babies with harmful exposure
In this way, the researchers identified molecular targets and mechanisms by which the mix of chemicals can influence brain development. “We found that the mixture interfered with the regulation of genes associated with autism, impeded the differentiation of neurons and altered the function of thyroid hormones in nerve tissue,” says Caporale’s colleague Giuseppe Testa. Based on the experimental studies, the researchers identified threshold values above which the combination of chemicals shows toxic properties. These are below the limit values set for the individual substances.
In the last step, the researchers compared the newly determined limit values with the concentrations measured in the blood and urine samples of the pregnant women. “We found that up to 54 percent of children had prenatal exposures above experimentally derived levels of concern,” the authors write. Accordingly, children with high exposure had a 3.3-fold increased risk of developing language disorders compared to children with low exposure.
methodological weaknesses
“The study offers an interesting approach to bringing epidemiological data together with toxicology,” comments Marcel Leist, Professor of In Vitro Toxicology and Biomedicine at the University of Konstanz. “Epidemiological data alone always provide correlative connections. The inclusion of in vitro systems – as shown here using the example of brain organoids, tadpoles and fish – could provide better evidence of causal relationships here.”
However, the study has methodological weaknesses. According to Leist, for example, there are no validation tests that ensure that the observed effects are actually due to the chemical mix and not to individual components. Based on the data, Leist is also unable to understand the finding that 54 percent of the children from the cohort examined were exposed to potentially dangerous levels of EDCs. “It is not clear whether all children with speech disorders could really be correlated with the high values, and the methodology used does not allow these conclusions,” he says. “In my opinion, the study cannot make any quantitative statements about human risk. Of course, it keeps the discussion going.”
Source: Nicolò Caporale (European Institute of Oncology, Milan, Italy) et al., Science, doi: 10.1126/science.abe8244