Summary
Oral administration of teratogenic doses of retinoic acid to pregnant hamsters on day 10 of gestation is associated with dysmorphogenesis of the appendicular skeleton. During the 24h following retinoic acid treatment, the developing limb bud vasculature was disorganized, with blood vessels encroaching on areas where mesenchymal condensation of the skeletal blastemata normally occurs. Large, branching marginal folds and endothelial cell vesiculations protruded into the blood vessel lumina. It is suggested that the vascular changes observed may affect the concurrent early development of the skeleton and contribute to the skeletal malformation seen in near-term fetuses.
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Amprino, R., Malmberg, P.A.: Observations on the avascular cultures of the chick embryo limb bud. Acta Embryol. Exp. 1, 3–28 (1973)
Caplan, A.I.: The molecular basis for limb morphogenesis. Fifth International Conference on Birth Defects. Montreal 1977
Caplan, A.I., Koutroupas, S.: The control of muscle and cartilage development in the chick wing: the role of differential vascularization. J. Embryol. exp. Morph. 29, 571–583 (1973)
Fell, H.B., Dingle, J.T., Webb, M.: Studies on the mode of action of excess vitamin A. 4. The specificity of the effect on embryonic chick limb cartilage in culture and an isolated rat-liver lysosomes. Biochem. J. 83, 63–69 (1962)
Fraser, B.A.: The relationship of aberrant vasculogenesis to retinoic acid induced dysmelia in the hamster fetus. Fifth International Conference on Birth Defects. Montreal 1977
Fraser, B.A., Travill, A.A.: Ultrastructural observations on the morphogenesis of retinoic acid induced dysmelia in the hamster fetus. J. Anat. 122, 730 (1976)
Goodman, D.S., Smith, J.E., Hembry, R.M., Dingle, J.T.: Comparison of the effects of vitamin A and its analogues upon rabbit ear cartilage in organ culture and upon growth of the vitamin A deficient rat. J. Lipid Res. 15, 406–414 (1974)
Ito, Y., Zile, M., Deluca, H.F., Ahrens, H.M.: Metabolism of retinoic acid in vitamin A deficient rats. Biochim. Biophys. Acta 369, 338–350 (1974)
Jurand, A.: Early changes in limb buds of chick embryos after thalidomide treatment. J. Embryol. exp. Morph. 16, 289–300 (1966)
Kochhar, D.M.: Cellular basis of congenital limb deformity induced in mice by vitamin A. Proceedings of the Second International Conference on Morphogenesis and Malformation. Birth Defects: Original Article Series 13, 111–154 (1977)
Kochhar, D.M.: Transplacental passage of label after administration of 3H retinoic acid (vitamin A acid) to pregnant mice. Teratology 14, 53–64 (1976)
Kochhar, D.M.: The use of in vitro procedures in teratology. Teratology 11, 273–288 (1975)
Kochhar, D.M.: The role of altered metabolism of glycosaminoglycans in the production of experimentally produced congenital malformations. In: Symposium on Metabolic Pathways in Mammalian Embryos During Organogenesis and its Modification by Drugs: Berlin: Free University Press, p. 421–440 (1970)
Lorente, C.A., Miller, S.A.: Fetal and maternal vitamin A levels in tissues of hypervitaminotic A rats and rabbits. J. Nutr. 107, 1816–1821 (1977)
Merker, H., Stüttgen, G.: Electron microscopic findings after toxic doses of vitamin A acid in man. Acta Dermatovener, Suppl. 74, 64–72 (1975)
Morriss, G.M.: The ultrastructural effects of excess maternal vitamin A on the primitive streak stage rat embryo. J. Embryol. exp. Morph. 30, 219–242 (1973)
Neubert, D., Merker, H.J., Tapken, S.: Comparative studies on the prenatal development of mouse extremities in vivo and in organ culture. Naunyn Schmiedeberg's Arch. Pharmacol. 286, 251–270 (1974b)
Neubert, D.S., Tapken, S., Merker, H.J.: Induction of skeletal malformations in organ cultures of mammalian embryonic tissues. Naunyn Schmiedeberg's Arch. Pharmacol. 286, 271–282 (1974)
Reynolds, E.S.: The use of lead citrate at high pH as an electron opaque stain in electron microscopy. J. Cell Biol. 17, 208–213 (1963)
Scow, R.O., Blanchette-Mackie, E.J., Smith, L.C.: Role of capillary endothelium in the clearance of chylomicrons. Circ. Res. 39, 149–162 (1976)
Searls, R.L.: Development of the embryonic chick limb bud in avascular culture. Develop. Biol. 17, 382–399 (1968)
Seichert, V., Rychter, Z.: Vascularization of the developing anterior wing of the chick embryo. Folia morphol. 20, 352–361 (1972)
Senior, H.D.: The development of the human lower extremity. Amer. J. Anat. 25, 55–95 (1919)
Shenefelt, R.E.: Morphogenesis of malformations in hamsters caused by retinoic acid: relation to dose and stage at treatment. Teratology 5, 103–118 (1972)
Spurr, A.R.: A low viscosity exposy resin embedding medium for electron microscopy. J. Ultrastruct. Res. 26, 31–43 (1969)
Wolpert, L.: Mechanisms of limb development and malformation. Br. Med. Bull. 32, 65–70 (1976)
Yamawaki, H., Nakamura, H., Fujisawa, H., Yasuda, M.: Effects of maternal hypervitaminosis A upon developing mouse limb buds. I. Light microscopic investigation. Cong. Anom. 14, 13–22 (1974)
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Fraser, B.A., Travill, A.A. The relation of aberrant vasculogenesis to skeletal malformation in the hamster fetus. Anat. Embryol. 154, 111–120 (1978). https://doi.org/10.1007/BF00317958
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DOI: https://doi.org/10.1007/BF00317958