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Maria Wielsøe

Assessment of chemical mixtures using biomarkers of combined biological activity: A screening study in human placentas

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  • Andrea Rodríguez-Carrillo, Biosanitary Investigation Institute (IBS) of Granada, University Hospital and University of Granada, Granada, Spain., University of Granada, Center for Biomedical Research (CIBM), Department of Radiology and Physical Medicine, School of Medicine, University of Granada, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Spain
  • Anna Kjerstine Rosenmai, Technical University of Denmark and Copenhagen University, Denmark
  • Vicente Mustieles, Biosanitary Investigation Institute (IBS) of Granada, University Hospital and University of Granada, Granada, Spain., University of Granada, Center for Biomedical Research (CIBM), Department of Radiology and Physical Medicine, School of Medicine, University of Granada, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP)
  • ,
  • Stephan Couderq, Physiologie moléculaire et Adaptation, France
  • Jean-Baptiste Fini, Physiologie moléculaire et Adaptation, France
  • Fernando Vela-Soria, Biosanitary Investigation Institute (IBS) of Granada, University Hospital and University of Granada, Granada, Spain., University of Granada, Center for Biomedical Research (CIBM), Department of Radiology and Physical Medicine, School of Medicine, University of Granada, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Spain
  • Jose Manuel Molina-Molina, Biosanitary Investigation Institute (IBS) of Granada, University Hospital and University of Granada, Granada, Spain., University of Granada, Center for Biomedical Research (CIBM), Department of Radiology and Physical Medicine, School of Medicine, University of Granada, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Spain
  • Patricia Ferrando-Marco, Andalusian School of Public Health, Instituto De Investigación Biosanitaria Ibs, GRANADA, Spain., Spain
  • Maria Wielsøe
  • Manhai Long
  • Eva Cecilie Bonefeld-Jorgensen
  • Nicolás Olea, Biosanitary Investigation Institute (IBS) of Granada, University Hospital and University of Granada, Granada, Spain., University of Granada, Center for Biomedical Research (CIBM), Department of Radiology and Physical Medicine, School of Medicine, University of Granada, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Spain
  • Anne Marie Vinggaard, Technical University of Denmark and Copenhagen University, Denmark
  • Mariana F Fernández, Biosanitary Investigation Institute (IBS) of Granada, University Hospital and University of Granada, Granada, Spain., University of Granada, Center for Biomedical Research (CIBM), Department of Radiology and Physical Medicine, School of Medicine, University of Granada, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Spain

Humans are simultaneously exposed to complex mixtures of chemicals with limited knowledge on potential health effects, therefore improved tools for assessing these mixtures are needed. As part of the Human Biomonitoring for Europe (HBM4EU) Project, we aimed to examine the combined biological activity of chemical mixtures extracted from human placentas using one in vivo and four in vitro bioassays, also known as biomarkers of combined effect. Relevant endocrine activities (proliferative and/or reporter gene assays) and four endpoints were tested: the estrogen receptor (ER), androgen receptor (AR), and aryl hydrocarbon receptor (AhR) activities, as well as thyroid hormone (TH) signaling. Correlations among bioassays and their functional shapes were evaluated. Results showed that all placental extracts agonized or antagonized at least three of the abovementioned endpoints. Most placentas induced ER-mediated transactivation and ER-dependent cell proliferation, together with a strong inhibition of TH signaling and the AR transactivity; while the induction of the AhR was found in only one placental extract. The effects in the two estrogenic bioassays were positively and significantly correlated and the AR-antagonism activity showed a positive borderline-significant correlation with both estrogenic bioassay activities. However, the in vivo anti-thyroid activities of placental extracts were not correlated with any of the tested in vitro assays. Findings highlight the importance of comprehensively mapping the biological effects of "real-world" chemical mixtures present in human samples, through a battery of in vitro and in vivo bioassays. This approach should be a complementary tool for epidemiological studies to further elucidate the combined biological fingerprint triggered by chemical mixtures.

Original languageEnglish
JournalReproductive toxicology (Elmsford, N.Y.)
Volume100
Pages (from-to)143-154
ISSN0890-6238
DOIs
Publication statusPublished - Mar 2021

    Research areas

  • bioassay, biomarkers, chemical mixtures, combined effect, endocrine disruption, HBM4EU, placenta, reproduction

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