Childhood Exposure to Endocrine Disruptors is Associated with Relevant Molecular Signatures

Exposure to endocrine disruptors in childhood is associated with biologically relevant molecular signatures, some of them related to neurological and metabolic pathways, according to a study led by the Barcelona Institute for Global Health (ISGlobal), an institution supported by “la Caixa” Foundation. The findings, published in Environment International, provide insight into possible mechanisms by which these chemicals may affect our health.

Endocrine disrupting chemicals (EDCs) are, as the name suggests, chemicals that can interfere with the action of hormones. And they are all around us – in pesticides, plastics, pharmaceuticals, beauty products, contaminated soil, etc. Exposure among children is particularly worrying because they eat, drink and breathe more chemicals per body weight than adults.

“We need more evidence to understand the health effects of exposure to EDCs, particularly in childhood,” says ISGlobal researcher Lea Maitre. One way to do this is to identify changes at different molecular levels (e.g. DNA, protein and metabolites) using a multi-omics approach. In this study, ISGlobal researcher Lea Maitre and colleagues used such an approach to identify molecular signatures associated with exposure to EDCs. They focused on non-persistent EDCs, which do not accumulate in our bodies. These include parabens, phthalates, phenols and organophosphate pesticides.

Endocrine disruptors and reproducible molecular signatures

The study involved 156 children aged 6 to 11 from the HELIX project, which groups cohorts from five European countries (UK, France, Spain, Lithuania and Greece). The children were followed for two periods of one week each, about 6 months apart, during which blood and urine samples were collected, as well as data on exposures and behaviour. Twenty-two non-persistent EDCs were measured in urine samples, and the multi-omic profiles were measured in blood (DNA methylation, proteins and metabolites) and urine (metabolites).

“Our approach allows us to study interactions between the different omics layers (DNA, protein, metabolites) and thus get a clearer picture of possible biological pathways,” says Lorenzo Fabbri, first author of the study.

The analysis revealed 23 direct associations between EDCs and molecular signatures (11 for DNA methylation sites, 9 for metabolites in urine or blood, and 3 for proteins in blood) that were reproducible at both time points. Nine of these associations were supported by evidence from previous literature. For example, the pesticide DEP with serotonin, the antimicrobial compound triclosan with serotonin and leptin, the phthalate OH-MiNP with kynurenine (involved in serotonin synthesis), and certain phenols with a DNA methylation site associated with obesity. For three of the EDC-metabolite associations, there was a clear link with health outcomes: serotonin and kynurenine are involved in neuro-behavioural development, while leptin is involved in obesity and insulin resistance.

The authors conclude that further prospective studies are needed to better measure exposure to these ubiquitous endocrine disrupting chemicals and characterise their long-term health impact.

Reference

Fabbri L, Garlantézec R, Audouze K et al. Childhood exposure to non-persistent endocrine disrupting chemicals and multi-omic profiles: A panel study. Environ Int. 2023. https://doi.org/10.1016/j.envint.2023.107856