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

被引:12
作者
Rodriguez-Carrillo, Andrea [1 ,2 ,3 ,4 ]
Rosenmai, Anna Kjerstine [5 ]
Mustieles, Vicente [1 ,2 ,3 ,4 ]
Couderq, Stephan [6 ]
Fini, Jean-Baptiste [6 ]
Vela-Soria, Fernando [1 ,2 ,3 ,4 ]
Manuel Molina-Molina, Jose [1 ,2 ,3 ,4 ]
Ferrando-Marco, Patricia [3 ]
Wielsoe, Maria [7 ]
Long, Manhai [7 ]
Bonefeld-Jorgensen, Eva Cecilie [7 ,8 ]
Olea, Nicolas [1 ,2 ,3 ,4 ]
Vinggaard, Anne Marie [5 ]
Fernandez, Mariana F. [1 ,2 ,3 ,4 ]
机构
[1] Univ Granada, Ctr Biomed Res CIBM, Granada, Spain
[2] Univ Granada, Sch Med, Dept Radiol & Phys Med, Granada 18016, Spain
[3] Inst Invest Biosanitaria Ibs GRANADA, Granada, Spain
[4] Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Armilla 18100, Spain
[5] Tech Univ Denmark, Natl Food Inst, Div Diet Dis Prevent & Toxicol, DK-2800 Lyngby, Denmark
[6] Museum Natl Hist Nat, Dept Adaptat Vivant, Physiol Mol & Adaptat, UMR 7221 MNHN CNRS, F-75005 Paris, France
[7] Aarhus Univ, Ctr Arctic Hlth & Mol Epidemiol, Dept Publ Hlth, Aarhus, Denmark
[8] Univ Greenland, Greenland Ctr Hlth Res, Nuuk, Greenland
关键词
Endocrine disruption; Chemical mixtures; Biomarkers; Combined effect; Bioassay; Placenta; Reproduction; HBM4EU;
D O I
10.1016/j.reprotox.2021.01.002
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 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 es-trogenic 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 bio-logical 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.
引用
收藏
页码:143 / 154
页数:12
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