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

Abstract

The authors thank the European Union's Horizon 2020 research and innovation programme HBM4EU under Grant Agreement No. 733032 for its financial support. Vicente Mustieles and Stephan Couderq are under contract within the HBM4EU project. Additionally, we acknowledge the Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP), and the Instituto de Salud Carlos III (ISCIII) (FIS-PI16/01820 and FIS-PI16/01858). The authors also thank the ISCIII and "Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER) for the Sara Borrell postdoctoral research contract granted to F. Vela-Soria (grant no. CD17/00212), and the Spanish Ministry of Education for the predoctoral fellowship (FPU) granted to A. Rodríguez-Carrillo (FPU 16/03011). This article will be part of the doctoral thesis developed by Andrea Rodríguez-Carrillo in the context of the "Clinical Medicine and Public Health Program" of the University of Granada (Spain). The authors gratefully acknowledge the technical assistance of Birgitte Møller Plesning. ; 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 Bio-monitoring 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 above-mentioned endpoints. Most placentas induced ER-mediated transactivation and ER-dependent cell proliferation, together with a strong ...