Universität zu Köln

Colleoni, Silvia, Galli, Cesare, Gaspar, John Antony, Meganathan, Kesavan, Jagtap, Smita, Hescheler, Jurgen, Sachinidis, Agapios and Lazzari, Giovanna (2011). Development of a Neural Teratogenicity Test Based on Human Embryonic Stem Cells: Response to Retinoic Acid Exposure. Toxicol. Sci., 124 (2). S. 370 - 378. OXFORD: OXFORD UNIV PRESS. ISSN 1096-0929

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Abstract

The aim of this study was the development of an alternative testing method based on human embryonic stem cells for prenatal developmental toxicity with particular emphasis on early neural development. To this purpose, we designed an in vitro protocol based on the generation of neural rosettes, representing the in vitro counterpart of the developing neural plate and neural tube, and we challenged this complex cell model with retinoic acid (RA), a well-known teratogenic agent. The cells were exposed to different concentrations of RA during the process of rosettes formation. Morphological and molecular parameters were evaluated in treated as compared with untreated cells to detect both cytotoxicity and specific neural toxicity. Transcriptomic analysis was performed with microarray Affymetrix platform and validated by quantitative real-time PCR for genes relevant to early neural development such as HoxA1, HoxA3, HoxB1, HoxB4, FoxA2, FoxC1, Otx2, and Pax7. The results obtained demonstrated that neural rosette forming cells respond to RA with clear concentration-dependent morphological, and gene expression changes remarkably similar to those induced in vivo, in the developing neural tube, by RA exposure. This strict correspondence indicates that the neural rosette protocol described is capable of detecting specific teratogenic mechanisms causing perturbations of early neural development and therefore represents a promising alternative test for human prenatal developmental toxicity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Colleoni, Silvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Galli, Cesare UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaspar, John Antony UNSPECIFIED UNSPECIFIED UNSPECIFIED Meganathan, Kesavan UNSPECIFIED UNSPECIFIED UNSPECIFIED Jagtap, Smita UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Jurgen UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Lazzari, Giovanna UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-484588
DOI:	10.1093/toxsci/kfr245
Journal or Publication Title:	Toxicol. Sci.
Volume:	124
Number:	2
Page Range:	S. 370 - 378
Date:	2011
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1096-0929
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TUBE DEFECTS; EXPRESSION; DIFFERENTIATION; SPECIFICATION; DERIVATION; ROSETTES; GENES; MOUSE; FOXC1; LISTS Multiple languages Toxicology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48458