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Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells.

Authors :
Marikawa Y
Chen HR
Menor M
Deng Y
Alarcon VB
Source :
Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2020 Jan; Vol. 91, pp. 74-91. Date of Electronic Publication: 2019 Nov 08.
Publication Year :
2020

Abstract

Pluripotent stem cells recapitulate many aspects of embryogenesis in vitro. Here, we established a novel culture system to differentiate human embryonic stem cell aggregates (HESCA), and evaluated its utility for teratogenicity assessment. Culture of HESCA with modulators of developmental signals induced morphogenetic and molecular changes associated with differentiation of the paraxial mesoderm and neuroectoderm. To examine impact of teratogenic exposures on HESCA differentiation, 18 compounds were tested, for which adequate information on in vivo plasma concentrations is available. HESCA treated with each compound were examined for gross morphology and transcript levels of 15 embryogenesis regulator genes. Significant alterations in the transcript levels were observed for 94% (15/16) of the teratogenic exposures within 5-fold margin, whereas no alteration was observed for 92% (11/12) of the non-teratogenic exposures. Our study demonstrates that transcriptional changes in HESCA serve as predictive indicator of teratogenicity in a manner comparable to in vivo exposure levels.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1873-1708
Volume :
91
Database :
MEDLINE
Journal :
Reproductive toxicology (Elmsford, N.Y.)
Publication Type :
Academic Journal
Accession number :
31711903
Full Text :
https://doi.org/10.1016/j.reprotox.2019.10.004