Fertility and Sterility
Volume 89, Issue 6 , Pages 1781-1786 , June 2008

Hyperglycosylated human chorionic gonadotropin and the source of pregnancy failures

  • Yasushi Sasaki, M.D., Ph.D.
  • ,
  • Donald G. Ladner, M.D.
  • ,
  • Laurence A. Cole, Ph.D.

      Affiliations

    • Corresponding Author InformationReprint requests: Laurence A. Cole, Ph.D., Professor and Chief of Women's Health Research, Department of Obstetrics and Gynecology, MSC10 5580, 1 University of New Mexico, Albuquerque, NM 87131 (FAX: 505-272-3903).

Received 19 October 2006 ,Revised 5 March 2007 ,Accepted 5 March 2007.

References 

  1. Lockwood CJ. Prediction of pregnancy loss. Lancet. 2000;355:1292–1294
  2. Semprini AE, Simoni G. Not so inefficient reproduction. Lancet. 2000;356:257–258
  3. Norwitz ER, Schust DJ, Fisher SJ. Implantation and the survival of early pregnancy. N Engl J Med. 2001;345:1400–1408
  4. Kovats S, Main EK, Librach C, Stubblebine M, Fisher SJ, DeMars R. A class I antigen, HLA-G, expressed in human trophoblasts. Science. 1990;248:220–223
  5. Uehara Y, Minowa W, Mori C, Shiota J, Kuno T, Noda T, et al. Placental defect and embryonic lethality in mice lacking hepatocyte grow factor/scatter factor. Nature. 1995;373:702–705
  6. Psychoyos A. Uterine receptivity for nidation. Ann NY Acad Sci. 1986;476:36–42
  7. Enders AC. Trophoblast-uterine interactions in the first days of implantation: models for the study of implantation events in the human. Semin Reprod Med. 2000;18:255–263
  8. Pijnenborg R, Bland JM, Robertson WB, Dixon G, Brosens I. The pattern of interstitial trophoblastic invasion of the myometrium in early human pregnancy. Placenta. 1981;2:303–316
  9. Wilcox AJ, Baird DD, Weinberg CR. Time of implantation of the conceptus and loss of pregnancy. N Engl J Med. 1999;340:1796–1799
  10. Wilcox AJ, Baird DD, Dunson D, McChesney R, Weinberg CR. Natural limits of pregnancy testing in relation to the expected menstrual period. JAMA. 2001;286:1759–1761
  11. Elliott MM, Kardana A, Lustbader JW, Cole LA. Carbohydrate and peptide structure of the alpha- and beta-subunits of human chorionic gonadotropin from normal and aberrant pregnancy and choriocarcinoma. Endocrine. 1997;7:15–32
  12. Cole LA, Khanlian SA, Sutton JM, Davies S, Stephens ND. Hyperglycosylated hCG (invasive trophoblast antigen, ITA) a key antigen for early pregnancy detection. Clin Biochem. 2003;36:647–655
  13. Kovalevskaya G, Birken S, Kakuma T, O'Connor JF. Early pregnancy human chorionic gonadotropin (hCG) isoforms measured by an immunometric assay for choriocarcinoma-like hCG. J Endocrinol. 1999;161:99–106
  14. Kovalevskaya G, Birken S, Kakuma T, Ozaki N, Sauer M, Lindheim S, et al. Differential expression of human chorionic gonadotropin (hCG) glycosylation isoforms in failing and continuing pregnancies: preliminary characterization of the hyperglycosylated hCG epitope. J Endocrinol. 2002;172:497–506
  15. Kovalevskaya G, Genbacev O, Fisher SJ, Caceres E, O'Connor JF. Trophoblast origin of hCG isoforms: cytotrophoblasts are the primary source of choriocarcinoma-like hCG. Mol Cell Endocrinol. 2002;194:147–155
  16. Cole LA, Dai D, Butler SA, Leslie KK, Kohorn EI. Gestational trophoblastic diseases: 1. Pathophysiology of hyperglycosylated hCG. Gynecol Oncol. 2006;102:144–149
  17. O'Connor JF, Ellish N, Kakuma T, Schlatterer J, Kovalevskaya G. Differential urinary gonadotropin profiles in early pregnancy and early pregnancy loss. Prenat Diagn. 1998;18:1232–1240
  18. Sutton-Riley JM, Khanlian SA, Byrn FW, Cole LA. A single serum test for measuring early pregnancy outcome with high predictive value. Clin Biochem. 2006;39:682–687
  19. Cole LA, Khanlian SA, Riley JM, Butler SA. Hyperglycosylated hCG in gestational implantation and in choriocarcinoma and testicular germ cell malignancy tumorigenesis. J Reprod Med. 2006;51:919–929
  20. Lei ZM, Taylor DD, Gercel-Taylor C, Rao CV. Human chorionic gonadotropin promotes tumorigenesis of choriocarcinoma JAR cells. Troph Res. 1999;13:147–159
  21. Hamada AL, Nakabayashi K, Sato A, Kiyoshi K, Takamatsu Y, Laoag-Fernandez JB, et al. Transfection of antisense chorionic gonadotropin ß gene into choriocarcinoma cells suppresses the cell proliferation and induces apoptosis. J Clin Endocrinol Metab. 2005;90:4873–4879
  22. In:  Johnson MH,  Everitt BJ editor. Essential reproduction. 5th ed.. Oxford, United Kingdom: Blackwell; 2000;
  23. Cole LA, Sutton JM, Higgins TN, Cembrowski GS. Between-method variation in hCG test results. Clin Chem. 2004;50:874–882
  24. Zygmunt M, Herr F, Keller-Schoenwetter S, Kunzi-Rapp K, Munstedt K, Rao CV, et al. Characterization of human chorionic gonadotropin as a novel angiogenic factor. J Clin Endocrinol Metab. 2002;87:5290–5296
  25. Zhang J, Cao YJ, Zhao YG, Sang QX, Duan EK. Expression of matrix metalloproteinase-26 and tissue inhibitor of metalloproteinase-4 in human normal cytotrophoblast cells and a choriocarcinoma cell line, JEG-3. Mol Hum Reprod. 2002;8:659–666
  26. Shih IM, Kurman RJ. The pathology of intermediate trophoblastic tumors and tumor-like lesions. Intl J Gynecol Pathol. 2001;20:31–47
  27. Shih IM, Kurman RJ. Immunohistochemical localization of inhibin-alpha in the placenta and gestational trophoblastic lesions. Int J Gynecol Pathol. 1999;18:144–150
  28. Shih IM, Kurman RJ. New concepts in trophoblastic growth and differentiation with practical application for the diagnosis of gestational trophoblastic disease. Verh Dtsch Ges Pathol. 1997;81:266–272
  29. Charnock-Jones DS, Sharkey AM, Boocock CA, Ahmed A, Plevin R, Ferrara N, et al. Vascular endothelial growth factor receptor localization and activation in human trophoblast and choriocarcinoma cells. Biol Reprod. 1994;51:524–530
  30. Sanyal M, Das C. Collagenase-IV in human trophoblast invasion and differentiation. Indian J Biochem Biophys. 1997;34:220–225
  31. Winterhager E, Reuss B, Hellmann P, Spray DC, Gruemmer R. Gap junction and tissue invasion: a comparison of tumorigenesis and pregnancy. Clin Exp Pharmacol Physiol. 1996;23:1058–1061
  32. Jauniaux E, Poston L, Burton GJ. Placenta-related disease of pregnancy: involvement of oxidative stress and implications in human evolution. Hum Reprod Update. 2006;12:747–756
  33. Wright A, Zhou Y, Weier JF, Caceres E, Kapidzic M, Tabata T, et al. Trisomy 21 is associated with variable defects in cytotrophoblast differentiation along the invasive pathway. Am J Med Genet A. 2004;130:354–364
  34. Frendo JL, Muller F. Placenta and trisomy 21. Gynecol Obstet Fertil. 2001;29:538–544
  35. Frendo JL, Therond P, Bird T, Massin N, Muller F, Guibourdenche J, et al. Overexpression of copper zinc superoxide dismutase impairs human trophoblast cell fusion and differentiation. Endocrinology. 2001;142:3638–3648
  36. Cole LA, Shahabi S, Oz UA, Bahado-Singh RO, Mahoney MJ. Hyperglycosylated hCG (invasive trophoblast antigen) immunoassay: a new basis for gestational Down syndrome screening. Clin Chem. 1999;45:2109–2119
  37. Baillie P, Sandler SW, Kukard RF. Human chorionic gonadotropin (hCG) in threatened abortion. S Afr Med J. 1973;47:1293–1296
  38. Qureshi NS, Edi-Osagie EC, Ogbo V, Ray S, Hopkins RE. First trimester threatened miscarriage treatment with human chorionic gonodotrophins: a randomised controlled trial. BJOG. 2005;112:1536–1541

PII: S0015-0282(07)00545-6

doi: 10.1016/j.fertnstert.2007.03.010

Fertility and Sterility
Volume 89, Issue 6 , Pages 1781-1786 , June 2008