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.
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Dimopoulou, MyrtoVerhoef, Aart
Gomes, Caroline A
van Dongen, Catharina W
Rietjens, Ivonne M C M
Piersma, Aldert H
van Ravenzwaay, Bennard
Type
ArticleLanguage
en
Metadata
Show full item recordTitle
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.Published in
Toxicol Lett 2018; 286:10-21Publiekssamenvatting
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.PMID
29337257ae974a485f413a2113503eed53cd6c53
10.1016/j.toxlet.2018.01.009
Scopus Count
Collections
Related articles
- A transcriptomic approach for evaluating the relative potency and mechanism of action of azoles in the rat Whole Embryo Culture.
- Authors: Dimopoulou M, Verhoef A, Pennings JLA, van Ravenzwaay B, Rietjens IMCM, Piersma AH
- Issue date: 2017 Dec 1
- Gene regulation by morpholines and piperidines in the cardiac embryonic stem cell test.
- Authors: Mennen RH, Hallmark N, Pallardy M, Bars R, Tinwell H, Piersma AH
- Issue date: 2021 Dec 15
- Embryotoxic and pharmacologic potency ranking of six azoles in the rat whole embryo culture by morphological and transcriptomic analysis.
- Authors: Dimopoulou M, Verhoef A, Pennings JLA, van Ravenzwaay B, Rietjens IMCM, Piersma AH
- Issue date: 2017 May 1
- Evaluation of in vitro embryotoxicity tests for Chinese herbal medicines.
- Authors: Li L, Yin Tang L, Liang B, Wang R, Sun Q, Bik San Lau C, Chung Leung P, Fritsche E, Liebsch M, Seiler Wulczyn AEM, Spielmann H, Wang CC
- Issue date: 2019 Oct
- Relative embryotoxic potency of p-substituted phenols in the embryonic stem cell test (EST) and comparison to their toxic potency in vivo and in the whole embryo culture (WEC) assay.
- Authors: Strikwold M, Woutersen RA, Spenkelink B, Punt A, Rietjens IM
- Issue date: 2012 Sep 3