Organ Culture in Teratology

  • L. Saxén
  • M. Karkinen-Jääskeläinen
  • I. Saxén
Part of the Current Topics in Pathology book series (CT PATHOLOGY, volume 62)


Our present, still fragmentary knowledge of teratogens and teratogenesis is based on studies following two major methodologic lines, non-experimental, epidemiologic studies, and experimental, in vivo investigations. Both approaches are hampered by many limitations and shortcomings, the most obvious in the epidemiologic studies being the complicated study situation and the great number of confounding factors (Saxén, 1974), whereas the greatest difficulty in animal experiments is the inapplicability of the results to other species, including human embryos (Fraser, 1964). Hence, we need to explore alternative and complementary methods for testing various substances for teratogenicity and for studying the mechanisms of abnormal development. Tissue culture has now been used for decades in many fields of biomedical research and has proved a most valuable tool in the hands of skillful, critical scientists. In teratology, the method may also eliminate some of the difficulties and shortcomings of epidemiological and in vivo studies, but so far it has found only a limited number of applications in this field. Cell culture methods have recently become indispensable in diagnostic teratology but their use in basic studies is difficult. Here organ culture, which allows good differentiation, morphogenesis, and often functional maturation of embryonic tissues in vitro, might prove more useful.


Chick Embryo Cleft Palate Rubella Virus Lens Capsule Lens Fiber 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bevelander, G., Nakahara, H., Rolle, G.K.: The effect of tetracycline on the development of the skeletal system of the chick embryo. Develop. Biol. 2, 298–312 (1960).PubMedCrossRefGoogle Scholar
  2. Bevelander, G., Rolle, G.K., Cohlan, S.Q.: The effect of the administration of tetracycline on the development of teeth. J. dent. Res. 40, 1020–1024 (1961).CrossRefGoogle Scholar
  3. Biggers, J.D., Gwatkin, R.B.B., Heyner, S.: The growth of avian and mammalian tibiae on a relatively simple chemically defined medium. Exp. Cell Res. 25, 41–58 (1961).PubMedCrossRefGoogle Scholar
  4. Charles, D.: Placental transmission of antibiotics. J. Obstet. Gynaec. Brit. Emp. 61, 750–757 (1954).PubMedCrossRefGoogle Scholar
  5. Cohlan, S.Q., Bevelander, G., Tiamsic, T.: Growth inhibition of prematures receiving tetracycline. Amer. J. Dis. Child. 105, 453–461 (1963).Google Scholar
  6. Ebert, J.D., Wilt, F.H.: Animal viruses and embryos. Quart. Rev. Biol. 35, 261–312 (1960).PubMedCrossRefGoogle Scholar
  7. Fell, H.B.: Techniques of bone cultivation. In: Methods in Medical Research, Vol. IV (ed. M.B. Vissher), p. 234. Chicago: Year Book Medical Publishers Inc. 1951.Google Scholar
  8. Fell, B.B.: Changes in synthesis induced in organ cultures. In: Synthesis of Molecular and Cellular Structure (ed. D. Rudnick), pp. 139–160. New York: Ronald Press Co. 1961.Google Scholar
  9. Fraser, F.C.: The use of teratogens in the analysis of abnormal developmental mechanisms. In: First International Conference on Congenital Malformations (ed. M. Fishbein), pp. 179–186. Philadelphia: Lippincott 1961.Google Scholar
  10. Fraser, F.C.: Experimental teratogenesis in relation to congenital malformations in man. In: Second International Conference on Congenital Malformations (ed. M. Fishbein), pp. 277–287. New York: The International Medical Congress Ltd. 1964.Google Scholar
  11. Fraser, F.C.: Some genetic aspects of teratology. In: Teratology: Principles and Techniques (eds. J.G. Wilson, J. Warkany), pp. 21–28. Chicago: University of Chicago Press 1965.Google Scholar
  12. Fraser, F.C.: Gene-environmental interactions in the production of cleft palate. In: Methods for teratological studies in experimental animals and man (eds. H. Nishimura, J.R. Miller), pp. 34–49 Tokyo: Igaku Shoin 1969.Google Scholar
  13. Fraser, F.C., Fainstat, T.D.: Production of congenital defects in the offspring of pregnant mice treated with cortisone. Pediatrics 8, 527–533 (1951).PubMedGoogle Scholar
  14. Halme, J., Kivirikko, K.I., Kaitila, I., Saxén, L.: Effect of tetracycline on collagen biosynthesis in cultured embryonic bones. Biochem. Pharmacol. 18, 827–836 (1969).PubMedCrossRefGoogle Scholar
  15. Kaitila, I.: Effect of tetracycline in mineralization in cycloheximide-treated bones in vitro. Calcif. Tiss. Res. 7, 46–57 (1971a).CrossRefGoogle Scholar
  16. Kaitila, I.: The mechanism by which tetracycline hydrochloride inhibits mineralization in vitro. Biochim. biophys. Acta (Amst.) 244, 584–594 (1971b).Google Scholar
  17. Kaitila, I., Wartiovaara, J., Laitinen, O., Saxén, L.: The inhibitory effect of tetracycline on osteogenesis in organ culture. J. Embryol. exp. Morph. 23, 185–211 (1970).PubMedGoogle Scholar
  18. Kalter, H.: Interplay of intrinsic and extrinsic factors. In: Teratology: Principles and Techniques (eds. J.G. Wilson, J. Warkany), pp. 57–80. Chicago: University of Chicago Press 1965.Google Scholar
  19. Karkinen-Jääskeläinen, M.: Spatial and temporal restriction of mumps virus induced lesions in the developing chick lens. Acata path. microbiol. scand., Sect. A, Suppl. 243, 1–52 (1973).Google Scholar
  20. Karkinen-Jääskeläinen, M., Saxén, L., Vaheri, A., Leinikki, P.: Rubella cataract in vitro: Sensitive period of the developing human lens. J. exp. Med. 141, 1238–1248 (1975).PubMedCrossRefGoogle Scholar
  21. Katz, E.P.: The kinetics of mineralization in vitro. I. The nucleation properties of 640-Å collagen at 25°. Biochim. biophys. Acta (Amst.) 194, 121–129 (1969).Google Scholar
  22. Lahti, A., Antila, E., Saxén, L.: The effect of hydrocortisone on the closure of the palatal shelves in two inbred strains of mice in vivo and in vitro. Teratology 6, 37–42 (1972).PubMedCrossRefGoogle Scholar
  23. Lahti, A., Saxén, L.: Effect of hydrocortisone on the closure of palatal shelves in vivo and in vitro. Nature (Lond.) 216, 1217–1218 (1967).CrossRefGoogle Scholar
  24. Lash, J. W., Saxén, L.: Human teratogenesis: In vitro studies on thalidomide inhibited chondrogenesis. Develop. Biol. 28, 61–70 (1972).PubMedCrossRefGoogle Scholar
  25. Milch, R.A., Rall, D.P., Tobie, J.E.: Fluorescence of tetracycline antibiotics in bone. J. Bone Jt. Surg. 40A, 897–910 (1958).Google Scholar
  26. Moriarty, T.M., Weinstein, S., Gibson, R.S.: The development in vitro and in vivo of fusion of the palatal processes of rat embryos. J. Embryol. exp. Morph. 11, 605–619 (1963).PubMedGoogle Scholar
  27. Pourtois, M.: La fusion des cretes palatines et son alteration par quelques agents tératogènes. Arch. Biol. (Liège) 79, 105–179 (1968).Google Scholar
  28. Robertson, G.G., Williamson, A.P., Blattner, R.J.: Origin and development of lens cataracts in mumps-infected chick embryos. Amer. J. Anat. 115, 473–486 (1964).PubMedCrossRefGoogle Scholar
  29. Saxén, I.: Effect of hydrocortisone on the development in vitro of the secondary palate in two inbred strains of mice. Arch. oral Biol. 18, 1469–1479 (1973).PubMedCrossRefGoogle Scholar
  30. Saxén, L.: Tetracycline: Effect on osteogenesis in vitro. Science 149, 870–872 (1965).PubMedCrossRefGoogle Scholar
  31. Saxén, L.: Effect of tetracycline on osteogenesis in vitro. J. exp. Zool. 162, 269–294 (1966).CrossRefGoogle Scholar
  32. Saxén, L.: Population surveillance for birth defects. In: Birth defects (eds. A.G. Motulsky, W. Lenz), pp. 177–186. Amsterdam: Excerpta Medica Foundation 1974.Google Scholar
  33. Soxén, L., Kaitila, I.: The effect and mode of action of tetracycline on bone development in vitro. Advanc. exp. Med. 27, 205–218 (1972).Google Scholar
  34. Soxén, L., Koskimies, O., Lahti, A., Miettinen, H., Rapola, J., Wartiovaara, J.: Differentiation of kidney mesenchyme in an experimental model system. Advanc. Morphogenes. 7, 251–293 (1968).Google Scholar
  35. Soxén, L., Rapola, J.: Congenital defects. New York: Holt, Rinehart & Winston 1969.Google Scholar
  36. Soxén, L., Vainio, T., Toivonen, S.: Effect of polyoma virus on mouse kidney rudiment in vitro. J. nat. Cancer Inst. 29, 597–631 (1962).Google Scholar
  37. Simpson, D.M., Burnette, J.C., Bawden, J. W.: Maternal-fetal blood tetracycline levels in guinea pigs. J. oral. Therap. Pharmacol. 3, 403–408 (1967).Google Scholar
  38. Strangeways, T.S.P., Fell, H.P.: Experimental studies on the differentiation of embryonic tissues growing in vivo and in vitro. I. The development of the undifferentiated limbbud (a) when subsequently grafted into the postembryonic chick and (b) when cultivated in vitro. Proc. roy. Soc. B 99, 340–364 (1926).CrossRefGoogle Scholar
  39. Töndury, G., Smith, D. W.: Fetal rubella pathology. J. Pediat. 68, 867–879 (1966).PubMedCrossRefGoogle Scholar
  40. Trowell, O.A.: Problems in the maintenance of mature organs in vitro. In: La Culture Organotypique (ed. E. Wolff), pp. 237–249. Paris: C.N.R.S. 1961.Google Scholar
  41. Vainio, T., Soxén, L., Toivonen, S.: The acquisition of cellular resistance to polyoma virus during embryonic differentiation. Virology 20, 380–385 (1963).PubMedCrossRefGoogle Scholar
  42. Virtanen, I., Karkinen-Jääskeläinen, M., Soxén, L.: Ultrastructural characteristics of mumps virus replication in the cataracts of chick embryonic lens. Exp. Eye Res. 17, 463–472 (1973).PubMedCrossRefGoogle Scholar
  43. Walker, B.E., Fraser, F.C.: Closure of the secondary palate in three strains of mice. J. Embryol. exp. Morph. 4, 176–189 (1956).Google Scholar
  44. Walker, B.E., Fraser, F.C.: The embryology of cortisone-induced cleft palate. J. Embryol. exp. Morph. 5, 201–209 (1957).Google Scholar
  45. Wallman, I.S., Hilton, H.B.: Teeth pigmented by tetracycline. Lancet 1962 I, 827–829.CrossRefGoogle Scholar
  46. Wartiovaara, J., Soxén, L., Vainio, T.: Viral susceptibility and embryonic differentiation. V. Localization of virus-like particles in mouse kidney rudiment infected with polyoma virus. Acta path. microbiol. scand. 63, 72–78 (1965).PubMedGoogle Scholar
  47. Wessells, N.K.: Avian and mammalian organ culture. In: Methods in Developmental Biology (eds. F.H. Wilt, N.K. Wessells), pp. 445–456. New York: Thomas Y. Crowell Company 1967.Google Scholar
  48. Williamson, A.P., Blattner, R.J., Simonsen, L.: Cataracts following mumps virus in early chick embryos. Proc. Soc. exp. Biol. (N.Y.) 96, 224–228 (1957).Google Scholar

Copyright information

© Springer-Verlag Berlin-Heidelberg 1976

Authors and Affiliations

  • L. Saxén
  • M. Karkinen-Jääskeläinen
  • I. Saxén

There are no affiliations available

Personalised recommendations