1. From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- Author
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Nicolò Caporale, Michelle Leemans, Lina Birgersson, Pierre-Luc Germain, Cristina Cheroni, Gábor Borbély, Elin Engdahl, Christian Lindh, Raul Bardini Bressan, Francesca Cavallo, Nadav Even Chorev, Giuseppe Alessandro D’Agostino, Steven M. Pollard, Marco Tullio Rigoli, Erika Tenderini, Alejandro Lopez Tobon, Sebastiano Trattaro, Flavia Troglio, Matteo Zanella, Åke Bergman, Pauliina Damdimopoulou, Maria Jönsson, Wieland Kiess, Efthymia Kitraki, Hannu Kiviranta, Eewa Nånberg, Mattias Öberg, Panu Rantakokko, Christina Rudén, Olle Söder, Carl-Gustaf Bornehag, Barbara Demeneix, Jean-Baptiste Fini, Chris Gennings, Joëlle Rüegg, Joachim Sturve, and Giuseppe Testa
- Subjects
Thyroid Hormones ,Autism Spectrum Disorder ,Phthalic Acids ,Endocrine Disruptors ,Risk Assessment ,Article ,Xenopus laevis ,Neural Stem Cells ,Phenols ,Pregnancy ,Animals ,Humans ,Language Development Disorders ,Zebrafish ,Fluorocarbons ,Multidisciplinary ,Gene Expression Profiling ,Brain ,Estrogens ,Organoids ,Gene Ontology ,Gene Expression Regulation ,Neurodevelopmental Disorders ,Child, Preschool ,Prenatal Exposure Delayed Effects ,Female ,Transcriptome ,Locomotion - Abstract
Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio , as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay.
- Published
- 2022