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.

From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures / N. Caporale, M. Leemans, L. Birgersson, P.-. Germain, C. Cheroni, G. Borbely, E. Engdahl, C. Lindh, R.B. Bressan, F. Cavallo, N.E. Chorev, G.A. D'Agostino, S.M. Pollard, M.T. Rigoli, E. Tenderini, A.L. Tobon, S. Trattaro, F. Troglio, M. Zanella, A. Bergman, P. Damdimopoulou, M. Jonsson, W. Kiess, E. Kitraki, H. Kiviranta, E. Nanberg, M. Oberg, P. Rantakokko, C. Ruden, O. Soder, C.-. Bornehag, B. Demeneix, J.-. Fini, C. Gennings, J. Ruegg, J. Sturve, G. Testa. - In: SCIENCE. - ISSN 0036-8075. - 375:6582(2022 Feb 18), pp. eabe8244.1-eabe8244.16. [10.1126/science.abe8244]

From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures

N. Caporale
Primo
;
C. Cheroni;F. Cavallo;G.A. D'Agostino;M.T. Rigoli;S. Trattaro;F. Troglio;M. Zanella;G. Testa
2022

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.
Animals; Autism Spectrum Disorder; Brain; Child, Preschool; Endocrine Disruptors; Estrogens; Female; Fluorocarbons; Gene Expression Profiling; Gene Expression Regulation; Gene Ontology; Humans; Language Development Disorders; Locomotion; Neural Stem Cells; Neurodevelopmental Disorders; Organoids; Phenols; Phthalic Acids; Pregnancy; Risk Assessment; Thyroid Hormones; Transcriptome; Xenopus laevis; Zebrafish; Prenatal Exposure Delayed Effects
Settore BIO/11 - Biologia Molecolare
Settore BIO/13 - Biologia Applicata
Settore BIO/14 - Farmacologia
Settore MED/13 - Endocrinologia
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Settore BIO/10 - Biochimica
Settore VET/07 - Farmacologia e Tossicologia Veterinaria
   Modeling Disease through Cell Reprogramming: a Translational Approach to the Pathogenesis of Syndromes Caused by Symmetrical Gene Dosage Imbalances
   DISEASEAVATARS
   EUROPEAN COMMISSION
   FP7
   616441

   Novel Testing Strategies for Endocrine Disruptors in the Context of Developmental NeuroToxicity (ENDpoiNTs)
   ENDpoiNTs
   EUROPEAN COMMISSION
   H2020
   825759
18-feb-2022
Article (author)
File in questo prodotto:
File Dimensione Formato  
Caporale et al. Science 2022.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 2.77 MB
Formato Adobe PDF
2.77 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/919414
Citazioni
  • ???jsp.display-item.citation.pmc??? 51
  • Scopus 121
  • ???jsp.display-item.citation.isi??? 110
social impact