RT Journal Article
T1 Assessment of chemical mixtures using biomarkers of combined biological activity: A screening study in human placentas.
A1 Rodriguez-Carrillo, Andrea
A1 Rosenmai, Anna Kjerstine
A1 Mustieles, Vicente
A1 Couderq, Stephan
A1 Fini, Jean-Baptiste
A1 Vela-Soria, Fernando
A1 Molina-Molina, Jose Manuel
A1 Ferrando-Marco, Patricia
A1 Wielsøe, Maria
A1 Long, Manhai
A1 Bonefeld-Jorgensen, Eva Cecilie
A1 Olea, Nicolas
A1 Vinggaard, Anne Marie
A1 Fernandez, Mariana F
K1 Bioassay
K1 Biomarkers
K1 Chemical mixtures
K1 Combined effect
K1 Endocrine disruption
K1 HBM4EU
K1 Placenta
K1 Reproduction
AB 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.
PB Elsevier Inc.
YR 2021
FD 2021-01-04
LK http://hdl.handle.net/10668/16974
UL http://hdl.handle.net/10668/16974
LA en
NO Rodríguez-Carrillo A, Rosenmai AK, Mustieles V, Couderq S, Fini JB, Vela-Soria F, et al. Assessment of chemical mixtures using biomarkers of combined biological activity: A screening study in human placentas. Reprod Toxicol. 2021 Mar;100:143-154.
NO 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.
DS RISalud
RD Jul 29, 2025