Summary
Complete transposition of the great arteries (TGA) is inducible by treatment with all-trans retinoic acid in the ICR mouse. In this model, hypoplasia and dysplasia of the proximal outflow tract cushion tissue lead to non-spiral septation. In order to evaluate the effect of retinoic acid on the extracellular matrix of the cardiac outflow tract, we examined the distribution of collagen type I and hyaluronic acid, immunohistochemically, on days 8–9 of gestation. In controls, collagen type I fibrils ran mainly in a radial direction, extending towards the endocardium in the cardiac jelly of the proximal outflow tract. Also, a pair of longitudinal fiber bundles were formed stretching to the distal outflow tract. As for hyaluronic acid, intense staining was observed in the submyocardial and intermyocardial space of the outer curvature of the heart. On the other hand, in retinoic acid-treated embryos, the submyocardial radial fibrils or longitudinal fiber bundles of collagen type I were diminished, and irregular and dense deposits of collagen type I were observed along the endocardium. Furthermore, hyaluronic acid showed a loss of differential localization between the outer and inner curvature. Instead, irregular and intense staining was observed uniformly along the outflow myocardium. Thus, retinoic acid appeared to have perturbed the differentiation in the proximal outflow tract causing an altered organization of multiple extracellular matrix molecules, including collagen type I and hyaluronic acid, which led to an abnormal molecular network of the cardiac jelly in the cardiac outflow tract, abnormal septation and, further, to TGA or TGA-type anomalies.
Similar content being viewed by others
References
Van Praagh R, Layton WL, Van Praagh S (1980) The morphogenesis of normal and abnormal relationship between the great arteries and the ventricles: Pathologic and experimental data. In: Van Praagh R, Takao A (eds) Etiology and morphogenesis of congenital heart diseases: Causes and processes. Futura Publishing, New York, pp 401–421
Van Mierop LHS, Winglesworth FW (1963) Pathogenesis of transposition complexes. III. True transposition of the great vessels. Am J Cardiol 12:233–239
Asami I, Koizumi K (1984) The development of the aortic channel when it arises from the right ventricle: An analytical experimental approach to the morphogenesis of transposition of the great arteries. In: Nora JJ, Takao A (eds) Congenital heart disease: Causes and processes. Futura Publishing, New York, pp 531–542
Okamoto N (1980) Congenital anomalies of the heart: Embryologic, morphologic and experimental teratology. Igakushoin, Tokyo, pp 204–242
Yasui H, Nakazawa M, Morishima M, Miyagawa-Tomita S, Momma K (1995) Morphological observations on the pathogenetic process of the great arteries induced by retinoic acid in mice. Circulation 91:2478–2486
Yasui H, Morishima M, Nakazawa M, Ando M, Takao A, Aikawa E (1997) Cardiac outflow tract septation in the mouse model of transposition of the great arteries. Teratology 55:353–363
Nakajima Y, Morishima M, Nakazawa M, Momma K (1996) Inhibition of outflow cushion mesenchyme formation in retinoic acid-induced complete transposition of the great arteries. Cardiovasc Res 31:E77-E85
Nakajima Y, Hiruma T, Nakazawa M, Morishima M (1996) Hypoplasia of cushion ridges in the proximal outflow tract elicits formation of a right ventricle-to-aortic route in retinoic acid-induced complete transposition of the great arteries in the mouse: Scanning electron microscopic observations of corrosion cast models. Anat Rec 245:76–82
Pexieder T, Rousseil MP, Prados-Frutos JC (1992) Prenatal pathogenesis of the transposition of great arteries. In: Vogel M, Bühlmeyer K (eds) Transposition of the great arteries 25 years after Rashkind balloon septostomy. Steinkopff Verlag, Darmstadt, pp 11–27
Markwald RR, Fitzharris TP, Manasek FJ (1977) Structural development of endocardial cushions. Am J Anat 148:85–120
Thompson RP, Abercrombie V, Wong M (1987) Morphogenesis of the truncus arteriosus of the chick embryo heart: Movements of autoradiographic tatoos during septation. Anat Rec 218:434–440
Nakamura A, Manasek FJ (1978) Cardiac jelly fibrils: Their distribution and organization. Birth Defects XIV:229–250
Manasek FJ (1975) The extracellular matrix of the early embryonic heart. In: Lieberman M, Sano T (eds) Developmental and physiological correlates of cardiac muscle. Raven, New York, pp 1–20
Mayne R (1984) The different types of collagen and collagenous peptides. In: Trelstad RL (ed) The role of extracellular matrix in development. Alan R Liss, New York, pp 33–42
Sinning AR, Lepera RC, Markward RR (1988) Initial expression of type I procollagen in chick cardiac mesenchyme is dependent upon myocardial stimulation. Dev Biol 130:167–174
Markwald RR, Fitzharris TP, Bank H, Bernanke DH (1978) Structural analysis of the matrical organization of glycosaminoglycans in developing endocardial cushions. Dev Biol 62:292–316
Spicer AP, Augustine ML, McDonald JA (1996) Molecular cloning and characterization of a putative mouse hyaluronan synthase. J Biol Chem 271:23400–23406
Osmond MK, Butler AJ, Voon FCT, Bellairs R (1991) The effect of retinoic acid on heart formation in the early chick embryo. Development 113:1405–1417
Davis LA, Saddler TW (1981) Effect of vitamin A on endocardial cushion development in the mouse heart. Teratology 24:139–148
Balbas JAM, Gato A, Revuelta MIA, Pastor JF, Represa JJ, Barbosa E (1993) Retinoic acid induces changes in the rhombencephalic neural crest cell migration and extracellular matrix composition in chick embryos. Teratology 48:197–206
Hierck BP, Gittenberger-de Groot AC, van Iperen L, Brouwer A, Poelmann RE (1996) Expression of the beta 4 integrin subunit in the mouse heart during embryonic development: Retinoic acid advances beta 4 expression. Dev Dyn 207:89–103
Dersch H, Zile MH (1993) Induction of normal cardiovascular development in the vitamin A-deprived quail embryo by natural retinoids. Dev Biol 160:424–433
Tsuda T, Philp N, Zile MH, Linask KK (1996) Left-right asymmetric localization of flection in the extracellular matrix during heart looping. Dev Biol 173:39–50
Barry A (1948) The functional significance of the cadiac jelly in the tubular heart of the chick embryo. Anat Rec 102:289–298
Wu R, Wu MM (1986) Effects of retinoids on human bronchial epithelial cells: Differential regulation of hyaluronate synthesis and keratin protein synthesis. Cell Physiol 127:73–82
Margelin D, Medaisko C, Lombard D, Picard J, Fourtanier A (1996) Hyaluronic acid and dermatan sulfate are selectively stimulated by retinoic acid in irradiated and nonirradiated hairless mouse skin. J Invest Dermatol 106:505–509
Yoshikawa H, Kukita T, Kurisu K, Tashiro HJ (1987) Effect of retinoic acid on in vitro proliferation activity and glycosaminoglycan synthesis of mesenchymal cells from palatal shelves of mouse fetuses. Craniofac Genet Dev Biol 7:45–51
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yasui, H., Nakazawa, M., Morishima, M. et al. Altered distribution of collagen type I and hyaluronic acid in the cardiac outflow tract of mouse embryos destined to develop transposition of the great arteries. Heart Vessels 12, 171–178 (1997). https://doi.org/10.1007/BF02767045
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02767045