From cohorts to molecules: adverse impacts of endocrine disrupting mixtures
Open accessAbstract
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.
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The Caporale et al. (2022) study found that approximately half of the women were exposed to levels of chemicals that could compromise neurodevelopment in their child.
“The study found that approximately half of the women were exposed to levels of chemicals that could compromise neurodevelopment in their child.”
From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Caporale et al., 2022
The available indexed passages are repository metadata, including a project listing under the label “Abstract,” rather than the paper’s findings. Searches for the claimed approximately half of women and for a 50% chemical-mixture exposure associated with child neurodevelopment found no passage addressing the estimate. The claim cannot be verified from our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measuredThe Caporale et al. study does not tell what levels of chemicals the developing fetal brains were actually exposed to because the exposure was estimated from levels of chemicals in maternal blood.
“However, the study does not tell what levels of chemicals the developing fetal brains were actually exposed to because the exposure was estimated from levels of chemicals in maternal blood.”
From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Caporale et al., 2022
The indexed copy contains an IRIS repository record rather than passages describing the study’s exposure measurements; the “01 - Articolo su periodico” section lists a PDF but provides no methods or results (no page number). Searches for maternal-blood measurements and fetal-brain chemical concentrations found no passage establishing whether the study measured either, so the claim cannot be verified from this copy. (LLM, conf=0.73)
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- Authors
- Caporale, N., Leemans, M., Birgersson, L., Germain, P.-L., Cheroni, C., Borbély, G., Engdahl, E., Lindh, C., Bressan, R. B., Cavallo, F., Chorev, N. E., D’Agostino, G. A., Pollard, S. M., Rigoli, M. T., Tenderini, E., Tobon, A. L., Trattaro, S., Troglio, F., Zanella, M., Bergman, Å., Damdimopoulou, P., Jönsson, M., Kiess, W., Kitraki, E., Kiviranta, H., Nånberg, E., Öberg, M., Rantakokko, P., Rudén, C., Söder, O., Bornehag, C.-G., Demeneix, B., Fini, J.-B., Gennings, C., Rüegg, J., Sturve, J., & Testa, G.
- Affiliations
- University of Milan (IT)
- Centre National de la Recherche Scientifique (FR)
- University of Gothenburg (SE)
- European Institute of Oncology (IT)
- Swedish Toxicology Sciences Research Center (SWETOX), Södertälje, Sweden.
- Uppsala University (SE)
- Lund University (SE)
- Edinburgh Cancer Research (GB)
- Stockholm University (SE)
- Karolinska University Hospital (SE)
- University Hospital Leipzig (DE)
- Lab of Basic Sciences, Faculty of Dentistry, National and Kapodistrian University of Athens, 152 72 Athens, Greece.
- Finnish Institute for Health and Welfare (FI)
- Örebro University (SE)
- Karolinska Institutet (SE)
- Karlstad University (SE)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Caporale, Nicolò
- Leemans, Michelle
- Birgersson, Lina
- Germain, Pierre-Luc
- Cheroni, Cristina
- Borbély, Gábor
- Engdahl, Elin
- D’Agostino, Giuseppe Alessandro
- Zanella, Matteo
- Bergman, Åke
- Damdimopoulou, Pauliina
- Öberg, Mattias
- Bornehag, Carl-Gustaf
- Demeneix, Barbara
- Fini, Jean-Baptiste
- Gennings, Chris
- Rüegg, Joëlle
- Sturve, Joachim
- Testa, Giuseppe
- ORCID
- Caporale, Nicolò
- Leemans, Michelle
- Birgersson, Lina
- Germain, Pierre-Luc
- Cheroni, Cristina
- Engdahl, Elin
- Lindh, Christian
- Bressan, Raul Bardini
- Cavallo, Francesca
- Chorev, Nadav Even
- D’Agostino, Giuseppe Alessandro
- Pollard, Steven M.
- Rigoli, Marco Tullio
- Tenderini, Erika
- Tobon, Alejandro Lopez
- Trattaro, Sebastiano
- Troglio, Flavia
- Bergman, Åke
- Damdimopoulou, Pauliina
- Jönsson, Maria
- Kiess, Wieland
- Kitraki, Efthymia
- Kiviranta, Hannu
- Öberg, Mattias
- Rantakokko, Panu
- Rudén, Christina
- Söder, Olle
- Bornehag, Carl-Gustaf
- Demeneix, Barbara
- Fini, Jean-Baptiste
- Gennings, Chris
- Rüegg, Joëlle
- Sturve, Joachim
- Testa, Giuseppe
- Venue
- Science
- Published
- 2022-02-18
- Volume
- 375
- Issue
- 6582
- Pages
- eabe8244-eabe8244
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4220765784
- Cited by
- 368
- References
- 20
- Citations by year
- 2026: 77 · 2025: 87 · 2024: 75 · 2023: 66 · 2022: 49 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 3
- FWCI
- 27.18
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- Cancer Research UK (DRCNPG-Nov21\100002)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- endocrine disruptors, chemical mixtures, mixture risk assessment, prenatal exposure, language delay, brain organoids, Xenopus laevis, zebrafish, behavioral responses
- MeSH terms
- Autism Spectrum Disorder, Animals, Brain, Child, Preschool, Estrogens, Female, Fluorocarbons, Gene Expression Regulation, Humans, Language Development Disorders, Locomotion, Organoids, Phenols, Phthalic Acids, Pregnancy, Prenatal Exposure Delayed Effects, Thyroid Hormones, Xenopus laevis, Zebrafish, Risk Assessment, Gene Expression Profiling, Endocrine Disruptors, Neural Stem Cells, Transcriptome, Gene Ontology, Neurodevelopmental Disorders
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