Biochemical and Biological Problems and Pitfalls of Cell Culture for Prenatal Diagnosis

  • Barbara K. Burton
  • Albert B. Gerbie
  • Henry L. Nadler


The analysis of cultivated amniotic fluid cells has proved to be the most reliable tool for the prenatal diagnosis of chromosomal abnormalities and inborn errors of metabolism. It is of paramount importance that extreme caution be exercised in the interpretation of results obtained from the analysis of these cells. In many instances, a decision as to whether or not a pregnancy will be continued is based on the result of a single laboratory study. The responsibility entrusted to those involved in prenatal diagnostic studies is therefore great. It is essential that everyone involved in such studies be thoroughly familiar with the origin and morphology of normal amniotic fluid cells as well as their growth properties and cytogenetic and biochemical characteristics. The normal variability in each of these parameters must be well defined before the results obtained from a particular sample are assumed to represent fetal abnormality.


Amniotic Fluid Prenatal Diagnosis Inborn Error Normal Human Fibroblast Tissue Culture Condition 
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. Barile, M. F., 1968, Mycoplasma and cell cultures, Natl. Cancer Inst. Monogr. 29:201.PubMedGoogle Scholar
  2. Beaudet, A. L., and Nichols, Jr., B. L., 1976, Residual altered a-mannosidase in human mannosidosis, Biochem. Biophys. Res. Commun. 68:292.PubMedCrossRefGoogle Scholar
  3. Benson, P. F., Blunt, S., and Brown, S. P., 1973, Amniotic cell galactokinase activity: Stimulation by galactose. Lancet 1:106.PubMedCrossRefGoogle Scholar
  4. Booth, C. W., and Nadler, H. L., 1974, Demonstration of the heterozygous state in Hunter’s syndrome. Pediatrics 53:396.PubMedGoogle Scholar
  5. Butterworth, J., Sutherland, G. R., Broadhead, D. M., et al., 1974, Lysosomal enzyme levels in human amniotic fluid cells in tissue culture. III.β-Glucuronidase, N-acetyl-β -D-glucosaminidase, a-mannosidase and acid phosphatase, Clin. Genet. 5:356.PubMedCrossRefGoogle Scholar
  6. Cox, R. P., and Gesner, B. M., 1965, Effect of simple sugars on the morphology and growth pattern of mammalian cell cultures, Proc. Natl. Acad. Sci. 54:1571.PubMedCrossRefGoogle Scholar
  7. Fogh, J., and Fogh, H., 1967, Irreversibility of major chromosome changes in a mycoplasmamodified line of FL human amnion cells, Proc. Soc. Exp. Biol. Med. 126:67.Google Scholar
  8. Fogh, J., and Fogh, H., 1968, Karyotypic changes in mycoplasma-modified lines of FL human amnion cells, Proc. Soc. Exp. Biol. Med. 129:944.PubMedGoogle Scholar
  9. Fogh, J., Holmgren, N. B., and Ludovici, P. P., 1971, A review of cell culture contaminations. In Vitro 7:26.PubMedCrossRefGoogle Scholar
  10. Galjaard, H., Van Hoogstraten, J. J., De Josselin De Jong, J. E., et al., 1974, Methodology of the quantitative cytochemical analysis of single or small numbers of cultured cells, Histochem. J. 6:409.PubMedCrossRefGoogle Scholar
  11. Gerbie, A. B., Nadler, H. L., and Gerbie, M. V., 1971, Amniocentesis in genetic counseling. Am. J. Obstet. Gynecol. 109:765.PubMedGoogle Scholar
  12. Gerbie, A. B., Melancon, S. B., Ryan, C. A., et al., 1972, Cultivated epithelial-like cells and fibroblasts from amniotic fluid: Their relationship to enzymatic and cytologic analysis. Am. J. Obstet. Gynecol. 114:314.PubMedGoogle Scholar
  13. Hoehn, H., Bryant, E. M., Karp, L. E., et al., 1974, Cultivated cells from diagnostic amniocentesis in second trimester pregnancies. I. Clonal morphology and growth potential, Pediat. Res. 8:746.PubMedCrossRefGoogle Scholar
  14. Hoehn, H., Bryant, E. M., Karp, L. E., et al., 1975, Cultivated cells from diagnostic amniocentesis in second trimester pregnancies. II. Cytogenetic parameters as functions of clonal type and preparative technique, Clin. Genet. 7:29.PubMedCrossRefGoogle Scholar
  15. Kaback, M. M., and Leonard, C. O., 1972, Morphological and enzymological considerations in antenatal diagnosis, in: Antenatal Diagnosis, (A. Dorfman, ed.), pp. 81–94, University of Chicago Press, Chicago.Google Scholar
  16. Kaback, M. M., Leonard, C. O., and Parmley, T. H., 1971, Intrauterine diagnosis: Comparative enzymology of cells cultivated from maternal skin, fetal skin, and amniotic fluid cells, Pediat. Res. 5:366.PubMedCrossRefGoogle Scholar
  17. Levine, E. M., Thomas, L., McGregor, D., et al., 1968, Altered nucleic acid metabolism in human cell cultures infected with mycoplasma, Proc. Natl. Acad. Sci. 60:583.PubMedCrossRefGoogle Scholar
  18. Lie, S. O., McKusick, V. A., and Neufeld, E. F., 1972, Simulation of genetic mucopolysaccharidoses in normal human fibroblasts by alterations of pH of the medium, Proc. Natl. Acad. Sci. 69:2361.PubMedCrossRefGoogle Scholar
  19. Lie, S. O., Schofield, B. H., Taylor, Jr., H. A., et al., 1973, Structure and function of the lysosomes of human fibroblasts in culture: Dependence on medium pH, Pediat. Res. 7:13.PubMedCrossRefGoogle Scholar
  20. Litwin, J., 1974, Growth of human diploid fibroblasts in media with different amino acid composition, J.Cell Sci. 14:671.PubMedGoogle Scholar
  21. Melancon, S. B., Lee, S. Y., and Nadler, H. L., 1971, Histidase activity in cultivated amniotic fluid cells, Science 173:627.PubMedCrossRefGoogle Scholar
  22. Nadler, H. L., 1968, Patterns of enzyme development utilizing cultivated human fetal cells derived from amniotic fluid, Biochem. Genet. 2:119.PubMedCrossRefGoogle Scholar
  23. Nadler, H. L., and Gerbie, A. B., 1970, Role of amniocentesis in the intrauterine diagnosis of genetic disorders, N. Engl. J. Med. 282:596.PubMedCrossRefGoogle Scholar
  24. National Amniocentesis Registry—A Collaborative Study sponsored by The National Institute of Child Health and Human Development of The National Institutes of Health, Bethesda, Md.Google Scholar
  25. Nelson, M. M., and Emery, A. E. H., 1973, Amniotic fluid cell cultures, J. Med. Genet. 10:19.PubMedCrossRefGoogle Scholar
  26. NICHD National Registry for Amniocentesis Study Group, 1976, Midtrimester amniocentesis for prenatal diagnosis, JAMA 236:1471.CrossRefGoogle Scholar
  27. Ogita, S., Matsumoto, M., and Sugawa, T., 1972, Maternal serum for the culture of amniotic fluid cells. Acta Obstet. Gynaecol. Japon. 19:266.Google Scholar
  28. Ryan, C. A., Lee, S. Y., and Nadler, H. L., 1972, Effect of culture conditions on enzyme activities in cultivated human fibroblasts, Exp. Cell Res. 71:388.PubMedCrossRefGoogle Scholar
  29. Schneider, E. L., and Stanbridge, E. J., 1975, Comparison of methods for the detection of mycoplasmal contamination of cell cultures: A review. In Vitro 11:20.PubMedCrossRefGoogle Scholar
  30. Schneider, E. L., Stanbridge, E. J., Epstein, C. J., et al., 1974, Mycoplasma contamination of cultured amniotic fluid cells: Potential hazard to prenatal chromosomal diagnosis. Science 184:477.PubMedCrossRefGoogle Scholar
  31. Shih, V. E., and Littlefield, J. W., 1970, Argininosuccinase activity in amniotic fluid cells. Lancet 2:45.PubMedCrossRefGoogle Scholar
  32. Shih, V. E., and Schulman, J. D., 1970, Ornithine ketoacid transaminase activity in human skin and amniotic fluid cell culture, Clin. Chim. Acta 27:73.PubMedCrossRefGoogle Scholar
  33. Sutherland, G. R., and Bain, A. D., 1973, Antenatal diagnosis of inborn errors of metabolism: Tissue culture aspects, Humangenetik 20:251.PubMedCrossRefGoogle Scholar
  34. Sutherland, G. R., Butterworth, J., Broadhead, D. M., et al., 1974a, Lysosomal enzyme variations in thirteen cell strains cultured from one amniotic fluid, Clin. Chim. Acta 52:211.PubMedCrossRefGoogle Scholar
  35. Sutherland, G. R., Butterworth, J., Broadhead, D. M., et al., 1974b, Lysosomal enzyme levels in human amniotic fluid cells in tissue culture. II. a-Galactosidase,)3-galactosidase and aarabinosidase, Clin. Genet. 5:351.PubMedCrossRefGoogle Scholar
  36. Sutherland, G. R., Bauld, R., and Bain, A. D., 1974c, Observations on human amniotic fluid cell strains in serial culture, J. Med. Genet. 11:190.PubMedCrossRefGoogle Scholar
  37. Uhlendorf, B. W., and Mudd, S. H., 1968, Cystathionine synthase in tissue culture derived from human skin: Enzyme defect in homocystinuria. Science 160:1007.PubMedCrossRefGoogle Scholar
  38. Welch, A. B., 1971, Selected enzyme activities and isoenzyme patterns of virus-infected cell cultures, J. Exp. Biol. Med. 137:702.Google Scholar
  39. Wood, S., 1975, The effect of environmental pH upon acid hydrolase activities of cultured human diploid fibroblasts, Exp. Cell Res. 96:317.PubMedCrossRefGoogle Scholar

Copyright information

© Aubrey Milunsky 1979

Authors and Affiliations

  • Barbara K. Burton
    • 1
  • Albert B. Gerbie
    • 2
    • 3
  • Henry L. Nadler
    • 4
    • 5
  1. 1.Department of Pediatrics, Division of GeneticsBowman Gray School of MedicineWinston-SalemUSA
  2. 2.Department of Obstetrics-GynecologyNorthwestern University Medical SchoolUSA
  3. 3.Department of Obstetrics-GynecologyThe Prentice Women’s HospitalChicagoUSA
  4. 4.Department of PediatricsNorthwestern University Medical SchoolChicagoUSA
  5. 5.Children’s Memorial HospitalChicagoUSA

Personalised recommendations