The impact of common endocrine disrupting chemicals on brain development

A mixture of chemicals commonly detected in human amniotic fluid has been found to perturb thyroid signalling, development of neurons and glia in the brain, and behavioural outcomes in offspring, when tested in a frog model of embryogenesis. The findings show the exquisite sensitivity of the developing organism to environmental contaminants.

Environmental chemicals are implicated as factors contributing to the increased prevalence of neurodevelopmental disorders 1. However, whether the environment has a causal role in the development of autism spectrum disorders, attention-deficit/hyperactivity disorder or other neurodevelopmental disorders is unclear. One reason for the con- troversy is that the human evidence is based on correlations between tissue concentrations of chemicals and neurobehavioural outcomes, each assessed at one or few times in an individual’s life. These studies cannot account for the real-world situation: that is, all wildlife, including humans, come into contact with a large number of chemicals in various mixtures, dosages and via different routes throughout their lives. Furthermore, dynamic changes in cellular and organ physiology in early life mean that even very low-level exposure to chemicals during sensitive periods might permanently change the developmental trajectory and lead to long-lasting dysfunction. This concept is particularly important when endocrine- disrupting chemicals (EDCs), defined as exogenous chemicals that interfere with any aspect of hormone action, are in the mix2. The endocrine system has a key role in determining how an organism responds and adapts to its environment. Disruptions to hormone signalling and metabolism, and actions of hormones on their receptors, potentially underlie the pathophysiological changes caused by exposures to EDCs 3.

“Exposure to multiple chemicals is inevitable… we live in a chemical soup..” – Linda Birnbaum (NIEHS)

The recent study by Fini, Bilal and colleagues demonstrates the power of a free-living embryonic model in assessing changes to early neurodevelopment and behaviour induced by exposure to a mixture of human-relevant environmental contaminants that perturb thyroid signalling 4.

In mammals, a pregnant mother’s exposure to the external world can inadvertently introduce EDCs into the exquisitely calibrated environment that comprises an embryo’s own hormones, together with maternal and placental hormones. Owing to the key impor- tance of proper thyroid hormone signalling in neurodevelopment, Fini and colleagues tested 15 chemicals found ubiquitously in the amniotic fluid of pregnant women in the USA for thyroid-disrupting activity. By using realistic exposure levels, and testing chemicals individually and in mixtures, the investigators have considerably advanced previous work in this area.

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Embryonic xenopus brains (1 week post fertilization), treated or untreated with the mixture of 15 chemicals. (Upper panel) The mixture exposure results in a reduction of neuron number and volume, and a reduction in oligodendrocyte volume. (Lower panel) The mixture exposure increases the number of proliferating cells. © Scientific Reports

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