Chimerism pp 3-17 | Cite as

Fertilization and Early Embryonic Errors

  • Nicole L. DraperEmail author
  • Kristy Crooks


Whole-body chimeras arise due to aberrant processes during fertilization and early embryogenesis. The genetically distinct cell populations may be distributed through the organism in varying relative proportions in different tissues giving rise to highly variably manifestations of chimerism. In many cases several equally valid mechanisms could have resulted in the observed genetic abnormalities. Cases of individuals with distinct cell lines may represent true chimerism and true mosaicism or may be considered on a spectrum in between the two. Dispermic chimeras have to date been the most widely identified group of whole-body chimeras because the distinct genetic contribution from the two sperm is quite easily identified.


Chimerism Fertilization Embryogenesis 


  1. 1.
    Gartler SM, Waxman SH, Giblett E. An XX/XY human hermaphrodite resulting from double fertilization. Proc Natl Acad Sci U S A. 1962;48:332–5.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Ramsay M, Pfaffenzeller W, Kotze E, et al. Chimerism in black southern African patients with true hermaphroditism 46,XX/47XY,+21 and 46,XX/46,XY. Ann N Y Acad Sci. 2009;1151:68–76.PubMedCrossRefGoogle Scholar
  3. 3.
    Verkauskas G, Jaubert F, Lortat-Jacob S, et al. The long-term followup of 33 cases of true hermaphroditism: a 40-year experience with conservative gonadal surgery. J Urol. 2007;177(2):726–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Berger-Zaslav A, Mehta L, Jacob J, et al. Ovotesticular disorder of sexual development (true hermaphroditism). Urology. 2009;73(2):293–6.PubMedCrossRefGoogle Scholar
  5. 5.
    James PA, Rose K, Francis D, Norris F. High-level 46XX/46XY chimerism without clinical effect in a healthy multiparous female. Am J Med Genet A. 2011;155A(10):2484–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Minelli A, Guala A, Groppo A, et al. Mechanism of origin in two cases of chimerism. Open J Pediatr. 2011;1:79–86. Scholar
  7. 7.
    Souter VL, Parisi MA, Nyholt DR, et al. A case of true hermaphroditism reveals an unusual mechanism of twinning. Hum Genet. 2007;121(2):179–85.PubMedCrossRefGoogle Scholar
  8. 8.
    Rodriguez-Buritica D, Rojnueangnit K, Messiaen LM, et al. Sex-discordant monochorionic twins with blood and tissue chimerism. Am J Med Genet A. 2015;167A(4):872–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Lucon DR, Zanchetta LM, Cavalcanti DP. Chimerism 47,XY,+21/46,XX in a female infant with anencephaly and other congenital defects. Genet Mol Biol. 2006;29(1):36–7.CrossRefGoogle Scholar
  10. 10.
    Malan V, Gesny R, Morichon-Delvallez N, et al. Prenatal diagnosis and normal outcome of a 46,XX/46,XY chimera: a case report. Hum Reprod. 2007;22(4):1037–41.PubMedCrossRefGoogle Scholar
  11. 11.
    Simon-Bouy B, Plachot M, Mokdad A, et al. Possible human chimera detected prenatally after in vitro fertilization: a case report. Prenat Diagn. 2003;23(11):935–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Yu N, Kruskall MS, Yunis JJ, et al. Disputed maternity leading to identification of tetragametic chimerism. N Engl J Med. 2002;346(20):1545–52.PubMedCrossRefGoogle Scholar
  13. 13.
    Draper N, Conley C, Smith C, Benson K. Dispermic chimerism identified during HLA typing for stem cell transplantation. Transfusion. 2008;48(7):1398–402.PubMedCrossRefGoogle Scholar
  14. 14.
    Castella V, Lesta Mdel M, Mangin P. One person with two DNA profiles: a(nother) case of mosaicism or chimerism. Int J Legal Med. 2009;123(5):427–30.PubMedCrossRefGoogle Scholar
  15. 15.
    Sheets K, Baird M, Heinig J, Davis D, Sabatini M, Starr D. A case of chimerism-induced paternity confusion: what ART practitioners can do to prevent future calamity for families. J Assist Reprod Genet. 2018;35(2):345–52.PubMedCrossRefGoogle Scholar
  16. 16.
    Rogol AD, Pieper LP. Genes, gender, hormones, and doping in sport: a convoluted tale. Front Endocrinol. 2017;8:251.CrossRefGoogle Scholar
  17. 17.
    Pruss A, Heymann GA, Hell A, et al. Acute intravascular hemolysis after transfusion of a chimeric RBC unit. Transfusion. 2003;43(10):1449–51.PubMedCrossRefGoogle Scholar
  18. 18.
    McFadden DE, Jiang R, Langlois S, Robinson WP. Dispermy--origin of diandric triploidy: brief communication. Hum Reprod. 2002;17(12):3037–8.PubMedCrossRefGoogle Scholar
  19. 19.
    McFadden DE, Robinson WP. Phenotype of triploid embryos. J Med Genet. 2006;43(7):609–12.PubMedCrossRefGoogle Scholar
  20. 20.
    Golubovsky MD. Postzygotic diploidization of triploids as a source of unusual cases of mosaicism, chimerism and twinning. Hum Reprod. 2003;18(2):236–42.PubMedCrossRefGoogle Scholar
  21. 21.
    Malan V, Vekemans M, Turleau C. Chimera and other fertilization errors. Clin Genet. 2006;70(5):363–73.PubMedCrossRefGoogle Scholar
  22. 22.
    Schmerler S, Wessel GM. Polar bodies-more a lack of understanding than a lack of respect. Mol Reprod Dev. 2011;78(1):3–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Destouni A, Zamani Esteki M, Catteeuw M, et al. Zygotes segregate entire parental genomes in distinct blastomere lineages causing cleavage-stage chimerism and mixoploidy. Genome Res. 2016;26(5):567–78.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Van de Leur SJ, Zeilmaker GH. Double fertilization in vitro and the origin of human chimerism. Fertil Steril. 1990;54(3):539–40.PubMedCrossRefGoogle Scholar
  25. 25.
    Giltay JC, Brunt T, Beemer FA, et al. Polymorphic detection of a parthenogenetic maternal and double paternal contribution to a 46,XX/46,XY hermaphrodite. Am J Hum Genet. 1998;62(4):937–40.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Bromilow IM, Duguid J. The Liverpool Chimaera. Vox Sang. 1989;57(2):147–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Chen CP, Chern SR, Sheu JC, et al. Prenatal diagnosis, sonographic findings and molecular genetic analysis of a 46,XX/46,XY true hermaphrodite chimera. Prenat Diagn. 2005;25(6):502–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Cho D, Lee JS, Yazer MH, et al. Chimerism and mosaicism are important causes of ABO phenotype and genotype discrepancies. Immunohematology. 2006;22(4):183–7.PubMedGoogle Scholar
  29. 29.
    Cho D, Lee SK, Yazer MH, et al. A dispermic chimera with mixed field blood group B and mosaic 46,XY/47,XYY karyotype. J Korean Med Sci. 2007;22(3):553–6.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Cui Y, Zhu P, Ye X, et al. The mechanism of tetragametic chimerism in a true hermaphrodite with 46,XX/46,XY. Zhonghua Nan Ke Xue. 2004;10(2):107–12. [in Chinese].PubMedGoogle Scholar
  31. 31.
    Dewald G, Haymond MW, Spurbeck JL, Moore SB. Origin of chi46,XX/46,XY chimerism in a human true hermaphrodite. Science. 1980;207(4428):321–3.PubMedCrossRefGoogle Scholar
  32. 32.
    Hong X, Ying Y, Xu X, et al. A dispermic chimera was identified in a healthy man with mixed field agglutination reaction in ABO blood grouping and mosaic 46, XY/46, XX karyotype. Transfus Apher Sci. 2013;48(2):223–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Lee KF, Hsu CS, Kuo PL, et al. The identification of a spontaneous 47, XX, +21/46, XY chimeric fetus with male genitalia. BMC Med Genet. 2012;13:85. Scholar
  34. 34.
    Mifsud NA, Haddad AP, Hart CF, et al. Serologic investigations of a chimera. Immunohematology. 1999;15(3):100–4.PubMedGoogle Scholar
  35. 35.
    Mosebach M, Parkner A, Jakubiczka S, et al. Dispermic chimerism identified during blood group determination and HLA typing. Transfusion. 2006;46(11):1978–81.PubMedCrossRefGoogle Scholar
  36. 36.
    Repas-Humpe LM, Humpe A, Lynen R, et al. A dispermic chimerism in a 2-year-old Caucasian boy. Ann Hematol. 1999;78(9):431–4.PubMedCrossRefGoogle Scholar
  37. 37.
    Schoenle E, Schmid W, Schinzel A, et al. 46,XX/46,XY chimerism in a phenotypically normal man. Hum Genet. 1983;64(1):86–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Shin SY, Yoo HW, Lee B, et al. Identification of the mechanism underlying a human chimera by SNP array analysis. Am J Med Genet A. 2012;158A(9):2119–23.PubMedCrossRefGoogle Scholar
  39. 39.
    Tsuji A, Munakata E, Kita T, et al. DNA analysis of a case of so-called blood group chimerism. Nihon Holgaku Zasshi. 1996;50(1):17–22. [in Japanese].Google Scholar
  40. 40.
    Winberg J, Gustavsson P, Lagerstedt-Robinson K, et al. Chimerism resulting from parthenogenetic activation and dispermic fertilization. Am J Med Genet A. 2010;152A(9):2277–86.PubMedCrossRefGoogle Scholar
  41. 41.
    Xia X, Wang W, Li T, Li W, et al. A parthenogenetic maternal and double paternal contribution to an ovotesticular disorder of sex development. Mol Cytogenet. 2014;7(1):16. Scholar
  42. 42.
    Yang E, Marsh S, Chen P, Chen C, Chen S, Lin P. A dispermic chimerism detected in a Taiwanese potential unrelated hematopoietic stem cell donor. HLA. 2017;89(2):98–103.PubMedCrossRefGoogle Scholar
  43. 43.
    Zhu PY, Yan JM, Xue M, et al. A case of dispermic chimerism with normal phenotype identified during ABO blood grouping. Clin Lab. 2014;60(6):1049–54.PubMedGoogle Scholar
  44. 44.
    Dauber EM, Glock B, Mayr D, Mayr WR. A case of dispermic chimerism: importance of DNA polymorphisms. J Biol Regul Homeost Agents. 1999;13(1):51–3.PubMedGoogle Scholar
  45. 45.
    Farag TI, Al-Awadi SA, Tippett P, et al. Unilateral true hermaphrodite with 46,XX/46,XY dispermic chimerism. J Med Genet. 1987;24(12):784–6.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Fitzgerald PH, Donald RA, Kirk RL. A true hermaphrodite dispermic chimera with 46, XX and 46, XY karyotypes. Clin Genet. 1979;15(1):89–96.PubMedCrossRefGoogle Scholar
  47. 47.
    Mayr WR. Human chimerism. Rev Fr Transfus Immunohematol. 1981;24(1):19–26.PubMedCrossRefGoogle Scholar
  48. 48.
    Moores PP, Watkins WM, Greenwell P, et al. Zulu XX/XX dispermic chimaera from Natal with two populations of red blood cells and patchy skin pigmentation. Vox Sang. 1988;54(1):52–6.PubMedGoogle Scholar
  49. 49.
    Takizawa H, Nakamura I, Hirasawa Y, et al. Dispermic chimerism associated with dysgerminoma. Exp Clin Immunogenet. 1989;6(2):133–42.PubMedGoogle Scholar
  50. 50.
    Watkins WM, Yates AD, Greenwell P, et al. A human dispermic chimaera first suspected from analyses of the blood group gene-specified glycosyltransferases. J Immunogenet. 1981;8(2):113–28.PubMedCrossRefGoogle Scholar
  51. 51.
    Wiley JE, Madigan M, Christie JD, Smith AW. Dispermic chimerism with two abnormal cell lines, 47,XY, +21 and 47,XX, +12. Am J Med Genet. 2002;107(1):64–6.PubMedCrossRefGoogle Scholar
  52. 52.
    Kaiser-Rogers KA, McFadden DE, Livasy CA, et al. Androgenetic/biparental mosaicism causes placental mesenchymal dysplasia. J Med Genet. 2006;43(2):187–92.PubMedCrossRefGoogle Scholar
  53. 53.
    Makrydimas G, Sebire NJ, Thornton SE, et al. Complete hydatidiform mole and normal live birth: a novel case of confined placental mosaicism: case report. Hum Reprod. 2002;17(9):2459–63.PubMedCrossRefGoogle Scholar
  54. 54.
    Surti U, Hill LM, Dunn J, et al. Twin pregnancy with a chimeric androgenetic and biparental placenta in one twin displaying placental mesenchymal dysplasia phenotype. Prenat Diagn. 2005;25(11):1048–56.PubMedCrossRefGoogle Scholar
  55. 55.
    Lewis GH, DeScipio C, Murphy KM, et al. Characterization of androgenetic/biparental mosaic/chimeric conceptions, including those with a molar component. Int J Gynecol Pathol. 2013;32(2):199–214.PubMedCrossRefGoogle Scholar
  56. 56.
    Strain L, Warner JP, Johnston T, Bonthron DT. A human parthenogenetic chimaera. Nat Genet. 1995;11(2):164–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Conlin LK, Thiel BD, Bonnemann CG, et al. Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis. Hum Mol Genet. 2010;19(7):1263–75.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Yamazawa K, Nakabayashi K, Kagami M, et al. Parthenogenetic chimaerism/mosaicism with a Silver-Russell syndrome-like phenotype. J Med Genet. 2010;47(11):782–5.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Drexler C, Glock B, Vadon M, et al. Tetragametic chimerism detected in a healthy woman with mixed-field agglutination reactions in ABO blood grouping. Transfusion. 2005;45(5):698–703.PubMedCrossRefGoogle Scholar
  60. 60.
    Fairchild L. She’s her own twin. ABC NEWS. 15 Aug 2006.
  61. 61.
    Green AJ, Barton DE, Jenks P, et al. Chimaerism shown by cytogenetics and DNA polymorphism analysis. J Med Genet. 1994;31(10):816–7.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Strain L, Dean JC, Hamilton MP, Bonthron DT. A true hermaphrodite chimera resulting from embryo amalgamation after in vitro fertilization. N Engl J Med. 1998;338(3):166–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Uehara S, Nata M, Nagae M, et al. Molecular biologic analyses of tetragametic chimerism in a true hermaphrodite with 46,XX/46,XY. Fertil Steril. 1995;63(1):189–92.PubMedCrossRefGoogle Scholar
  64. 64.
    van Bever Y, Wolffenbuttel KP, Brüggenwirth HT, et al. Multiparameter investigation of a 46,XX/46,XY tetragametic chimeric phenotypical male patient with bilateral scrotal ovotestes and ovulatory activity. Sex Dev. 2018;12(1–3):145–54.PubMedCrossRefGoogle Scholar
  65. 65.
    Verdiani S, Bonsignore A, Casarino L, et al. An unusual observation of tetragametic chimerism: forensic aspects. Int J Legal Med. 2009;123(5):431–5.PubMedCrossRefGoogle Scholar
  66. 66.
    De la Chapelle A, Schroder J, Rantanen P, et al. Early fusion of two human embryos? Ann Hum Genet. 1974;38(1):63–75.PubMedCrossRefGoogle Scholar
  67. 67.
    Lipsker D, Flory E, Wiesel ML, et al. Between light and dark, the chimera comes out. Arch Dermatol. 2008;144(3):327–30.PubMedCrossRefGoogle Scholar
  68. 68.
    Nyberg RH, Haapala AK, Simola KO. A case of human chimerism detected by unbalanced chromosomal translocation. Clin Genet. 1992;42(5):257–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Verp MS, Harrison HH, Ober C, et al. Chimerism as the etiology of a 46,XX/46,XY fertile true hermaphrodite. Fertil Steril. 1992;57(2):346–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Zuelzer WW, Beattie KM, Reisman LE. Generalized unbalanced mosaicism attributable to dispermy and probable fertilization of a polar body. Am J Hum Genet. 1964;16(1):38–51.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Boklage CE. Survival probability of human conceptions from fertilization to term. Int J Fertil. 1990;35(2):75–94.PubMedGoogle Scholar
  72. 72.
    Boklage CE. Embryogenesis of chimeras, twins and anterior midline asymmetries. Hum Reprod. 2006;21(3):579–91.PubMedCrossRefGoogle Scholar
  73. 73.
    Irmak MK. Self-fertilization in human: having a male embryo without a father. Med Hypotheses. 2010;75(5):448–51.PubMedCrossRefGoogle Scholar
  74. 74.
    Boklage CE. Traces of embryogenesis are the same in monozygotic and dizygotic twins: not compatible with double ovulation. Hum Reprod. 2009;24(6):1255–66.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Wulfsberg EA, Wassel WC, Polo CA. Monozygotic twin girls with diploid/triploid chromosome mosaicism and cutaneous pigmentary dysplasia. Clin Genet. 1991;39(5):370–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologyUniversity of Colorado School of MedicineAuroraUSA
  2. 2.Transfusion ServicesUniversity of Colorado HospitalAuroraUSA
  3. 3.Colorado Center for Personalized Medicine BiobankAuroraUSA
  4. 4.Colorado Molecular Correlates LaboratoryAuroraUSA

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