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Induction of cardiac anomalies with all-trans retinoic acid in the chick embryo

Published online by Cambridge University Press:  19 August 2008

Monique L. A. Broekhuizen ,
Juriy W. Wladimiroff ,
Dick Tibboel ,
Robert E. Poelmann ,
Arnold C. G. Wenink  and
Adriana C. Gittenberger-de Groot
Monique L. A. Broekhuizen*
Affiliation:
From the Department of Obstetrics and Gynaecology, Sophia Children's Hospital, Erasmus University of Rotterdam, Rotterdam
Juriy W. Wladimiroff
Affiliation:
From the Department of Obstetrics and Gynaecology, Sophia Children's Hospital, Erasmus University of Rotterdam, Rotterdam
Dick Tibboel
Affiliation:
Department of Pediatric Surgery, Sophia Children's Hospital, Erasmus University of Rotterdam, Rotterdam
Robert E. Poelmann
Affiliation:
Department of Anatomy and Embryology, University of Leiden, Leiden
Arnold C. G. Wenink
Affiliation:
Department of Anatomy and Embryology, University of Leiden, Leiden
Adriana C. Gittenberger-de Groot
Affiliation:
Department of Anatomy and Embryology, University of Leiden, Leiden
*
Dr. Monique L. A. Broekhuizen, Department of Anatomy and Embryology, University of Leiden, P.O. Box 9602, 2300 RC Leiden, The Netherlands. Tel. 071-276691; Fax. 071-276680.
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Summary

To study the interaction between hemodynamics and morphology in abnormal development of the heart, it is essential to have an animal model with specific and reproducible cardiac malformations. A standardized method was developed for inducing such an anomaly in the chick embryo. For this purpose, all-trans retinoic acid, dissolved in 2% dimethylsulphoxide, was applied on the vitelline membrane of the embryo in concentrations of 1.0 μgm and 0.3 μgm. A total of 207 embryos, staged according to Hamburger and Hamilton, were treated at stages 10 (33 hours of incubation) and 15 (50–55 hours of incubation). Three control groups consisted of embryos solely treated with dimethylsulphoxide, sham operated chicks, and untreated embryos, respectively. The embryos were sacrificed on the 9th, 10th and 11th days of incubation and hearts were examined by microdissection. Additional histologic studies were undertaken in 110 cases. Embryos treated with retinoic acid at both stages of development showed a high percentage of lesions falling within the general spectrum of double outlet right ventricle. The abnormality varied from merely a rightward shift of the aorta to cases with an additional subaortic ventricular septal defect, which, in combination with the rightward positioned aorta, was classified as a double outlet right ventricle. Histologic examination showed the presence of muscular tissue between the leaflets of the aortic and mitral valves. No other types of cardiac malformations were seen. Our results, with respect to timing, resemble data from studies made of hearts after surgical ablation of neural crest at comparable stages. Both method and timing of treatment with retinoic acid are important factors for the induction of specific and reproducible cardiac anomalies. This chick model allows for further detailed study of development of double outlet right ventricle, as well as the assessment of early detectable hemodynamic changes.

Keywords

cardiac anomaliesall-trans retinoic acidexperimental embryologydouble-outlet right ventriclechick embryo
Type
Original Articles
Information
Cardiology in the Young , Volume 2 , Issue 4 , October 1992 , pp. 311 - 317
Copyright
Copyright © Cambridge University Press 1992

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