Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 534090
Title A comparison of the embryonic stem cell test and whole embryo culture assay combined with the BeWo placental passage model for predicting the embryotoxicity of azoles
Author(s) Dimopoulou, Myrto; Verhoef, Aart; Gomes, Caroline A.; Dongen, Catharina W. van; Rietjens, Ivonne M.C.M.; Piersma, Aldert H.; Ravenzwaay, Bennard van
Source Toxicology Letters 286 (2018). - ISSN 0378-4274 - p. 10 - 21.
DOI https://doi.org/10.1016/j.toxlet.2018.01.009
Department(s) ATV Toxicologie Postdoc
Sub-department of Toxicology
VLAG
WIMEK
Publication type Refereed Article in a scientific journal
Publication year 2018
Keyword(s) Azoles - Biomarkers - Embryotoxicity - Placental transfer - Stem cell test - Whole embryo culture
Abstract In the present study, we show the value of combining toxico-dynamic and -kinetic in vitro approaches for embryotoxicity testing of azoles. Both the whole embryo culture (WEC) and the embryonic stem cells test (EST) predicted the in vivo potency ranking of twelve tested azoles with moderate accuracy. Combining these results with relative placental transfer rates (Papp values) as determined in the BeWo cell culture model, increased the predictability of both WEC and EST, with R2 values increasing from 0.51 to 0.87 and from 0.35 to 0.60, respectively. The comparison of these in vitro systems correlated well (R2 = 0.67), correctly identifying the in vivo strong and weak embryotoxicants. Evaluating also specific gene responses related with the retinoic acid and sterol biosynthesis pathways, which represent the toxicological and fungicidal mode of action of azoles respectively in the WEC and EST, we observed that the differential regulation of Dhrs3 and Msmo1 reached higher magnitudes in both systems compared to Cyp26a1 and Cyp51. Establishing sensitive biomarkers across the in vitro systems for studying the underlying mechanism of action of chemicals, such as azoles, is valuable for comparing alternative in vitro models and for improving insight in the mechanism of developmental toxicity of chemicals.
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