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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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References

1.Clark, EB, Hu, N, Dummett, JL, Van, de Kieft GK, Olson, C, Tomanek, R. Ventricular function and morphology in chick embryo from stages 18–29. Am J Physiol 1983; 250: H407–H413.Google Scholar
2.Hu, N, Clark, EB. Hemodynamics of stage 12 to stage 29 chick embryos. Circulation Res 1989; 65: 1665–1670.CrossRefGoogle Scholar
3.Colvee, E, Hurle, JM. Malformations of the semilunar valves produced in chick embryos by mechanical interference with cardiogenesis. Anat Embryol 1983; 168: 59–71.CrossRefGoogle ScholarPubMed
4.Rychter, Z. Experimental morphology of the aortic arches and the heart loop in the chick embryo. Adv Morphol 1962; 2: 333–371.CrossRefGoogle Scholar
5.Loeber, CP, Hendrix, MJC, Pinos de, SD, Golberg, SJ. Trichlorethylene: A cardiac teratogen in developing chick embryos. Pediatr Res 1988; 24: 740–743.CrossRefGoogle Scholar
6.Pexieder, T. Teratogens. In: Pierpont, ME, Moller, JH, (eds). Genetics of cardiovascular disease. Martinus Nijhoff Publishing, Amsterdam, 1986.Google Scholar
7.Chytil, F. Retinoic acid: biochemistry, pharmacology, toxicology and therapeutic use. Pharm Reviews 1984; 36: 935–945.Google ScholarPubMed
8.Hart, RC, McCue, PA, Ragland, WL, Winn, KJ, Unger, ER. Avian model for 13-cis-retinoic acid embryopathy: demonstration of neural crest related defects. Teratology 1990; 41: 463–472.CrossRefGoogle Scholar
9.Jellinek, R, Kistler, A. Effect of retinoic acid upon the chick embryonic morphogenetic systems. The embryotoxicity range. Teratology 1981; 23: 191–195.CrossRefGoogle Scholar
10.Kawashima, H, Ohnol, , Ueno, Y, Nakaya, S, Kato, E, Taniguchi, N. Syndrome of microtia and aortic arch anomalies resembling isoretinoin embryopathy. J Pediatr 1987; 111: 738–740.CrossRefGoogle Scholar
11.Lammer, EJ, Chen, DT, Hoa, RM, Agnish, WD, Benke, PJ, Curry, C, Fernhoff, PM, Grix, AW, Lott, IT, Richard, JM, Sun, SC. Retinoic acid embryopathy. N Engl J Med 1985; 313: 837–841.CrossRefGoogle ScholarPubMed
12.Rosa, FW, Wil, AL, Kelsey, FO. Teratogen update. Vitamin A congeners. Teratology 1986; 33: 355–364.CrossRefGoogle ScholarPubMed
13.Yasuda, Y, Okamoto, M, Konishi, H, Matsuo, T, Kihara, T, Tanimura, T. Developmental anomalies induced by all-trans retinoic acid in fetal mice: 1. Macroscopic findings. Teratology 1986; 34: 37–49.CrossRefGoogle ScholarPubMed
14.Kirby, ML, Stewart, D. Neural crest origin of cardiac ganglion cells in the chick embryo: identification and extirpation. Dev Biol 1983; 97: 433–443.CrossRefGoogle ScholarPubMed
15.Kirby, ML. Cardiac morphogenesis-recent research advances. Pediatr Res 1987; 21: 219–224.CrossRefGoogle ScholarPubMed
16.Le, Douarin NM. The neural crest. CambridgeUniversity Press, 1982.Google Scholar
17.Kirby, ML. Nodose placode provides ectomesenchyme to the developing chick heart in the absence of the cardiac neural crest. Cell Tissue Res 1988; 252: 17–22.CrossRefGoogle Scholar
18.Kirby, ML, Waldo, L. Role of the neural crest in congenital heart disease. Circulation 1990; 82: 332–340.CrossRefGoogle ScholarPubMed
19.Nishibitake, M, Kirby, ML, van, Mierop L. Pathogenesis of persistent truncus arteriosus and dextroposed aorta in the chick embryo after neural crest ablation. Circulation 1987; 75: 255–264.CrossRefGoogle Scholar
20.Hamburger, V, Hamilton, HL. A series of normal stages in the development of the chick embryo. J Morph 1951; 88: 49–92.CrossRefGoogle ScholarPubMed
21.Sissman, NJ. Developmental landmarks in cardiac morphogenesis: comparative chronology. Am J Cardiol 1970; 25: 141–148.CrossRefGoogle ScholarPubMed
22.Hassel, JR, Greenberg, JH, Johnston, MC. Inhibition of cranial neural crest cell development by vitamin A in the cultured chick embryo. J Embryol Exp Morphol 1977; 39: 267–271.Google Scholar
23.Maden, M, Hunt, P, Eriksson, U, Kuroiwa, A, Krumlauf, R, Summerbell, D. Retinoic acid-binding protein, rhombomeres and the neural crest. Development 1991; 111: 35–44.CrossRefGoogle ScholarPubMed
24.Ruberte, E, Dolle, P, Chambon, P, Morriss-Kay, G. Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattern of transcription during early morphogenesis in mouse embryos. Development 1991; 111: 45–60.CrossRefGoogle ScholarPubMed
25.Taylor, IM. Some early effects of retinoic acid on the young hamster heart. In: Mechanisms of Cardiac Morphogenesis and Teratogenesis. Pexieder, T. (ed). Raven press, New York, 1981, Vol 5, pp 151–161.Google Scholar
26.de la Cruz, E, Sun, E, Vangvanichyakorn, K, Desposito, F. Multiple congenital malformations associated with maternal isoretinoin therapy. Pediatrics 1984; 74: 428–430.CrossRefGoogle Scholar
27.Vuillemin, M, Pexieder, T, Winking, H. Pathogenesis of various forms of double outlet right ventricle in mouse fetal trisomy 13. Int J Cardiol 1991; 281–304.CrossRefGoogle ScholarPubMed