Skip to main content
SpringerLink
Log in

A Seminar on Human Cloning: Cloning in Reproductive Medicine

  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

This review article summarizes the historical development of mammalian cloning, presents current advances and presumed risk factors in the field of reproductive cloning, discusses possible clinical applications of therapeutic and diagnostic cloning and outlines prospective commercial trends in pharmacytical cloning. Predictable progress in biotechnology and stem cell engineering should prove to be advantageous for patients' health and for novel benefits in reproductive and regenerative medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Illmensee K, Hoppe PC: Nuclear transplantation in Mus musculus: Developmental potential of nuclei from preimplantation embryos. Cell 1981;23:9-18

    Google Scholar 

  2. McGrath J, Solter D: Inability of mouse blastomere nuclei transferred to enucleated zygotes to support development in vitro. Science 1984;226:1317-1319

    Google Scholar 

  3. McLaren A: The decade of the sheep. How a discredited technique led to the potential for creating new species. Nature 2000;403:479-480

    Google Scholar 

  4. Willadsen SM: Nuclear transplantation in sheep embryos. Nature 1986;320:63-65

    Google Scholar 

  5. Prather RS, Barnes FL, First NL: Nuclear transplantation in the bovine embryo: Assessment of donor nuclei and recipient oocytes. Biol Reprod 1987;37:859-866

    Google Scholar 

  6. Prather RS, Sims MM, First NL: Nuclear transplantation in early pig embryos. Biol Reprod 1989;41:414-418

    Google Scholar 

  7. Zhang Y, Wang J, Qian J, Hao Z: Nuclear transplantation in goat embryos. Sci Agric Sin 1991;24:1-6

    Google Scholar 

  8. Hall JL, Gindoff PR, Stillman RJ: Use of the artificial zona pellucida and zona replacement in assisted reproduction. Assist Reprod Rev 1993;3:129-135

    Google Scholar 

  9. Cheong HAT, Takahashi Y, Kanagawa H: Birth of mice after transplantation of early cell-cycle stage embryo nuclei into enucleated oocytes. Biol Reprod 1993;48:958-963

    Google Scholar 

  10. Sims M, First NI: Production of calves by transfer of nuclei from cultured inner cell mass cells. Proc Natl Acad Sci USA 1994;91:6143-6247

    Google Scholar 

  11. Campbell KHS, McWhir J, Ritchie WA, Wilmut I: Sheep cloned by nuclear transfer from a cultured cell line. Nature 1996;380:64-66

    Google Scholar 

  12. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KHS: Viable offspring derived from fetal and adult mammalian cells. Nature 1997;385:810-813

    Google Scholar 

  13. Wells DN, Misica PM, Day AM, Tervit HR: Production of cloned lambs from an established embryonic cell line: A comparison between in vitro-and in vitro-matured cytoplasts. Biol Reprod 1997;57:385-393

    Google Scholar 

  14. Meng L, Ely JJ, Stouffer RL, Wolf DP: Rhesus monkeys produced by nuclear transfer. Biol Reprod 1997;57:454-459

    Google Scholar 

  15. Tsunoda Y, Kato Y: Not only inner cell nuclei but also trophectoderm nuclei of mouse blastocysts have a developmental totipotency. J Reprod Fertil 1998;113:181-184

    Google Scholar 

  16. Kato Y, Tani T, Sotomaru Y, Kurokawa K, Kato J, Doguchi H, Yasue H, Tsunoda Y: Eight calves cloned from somatic cells of a single adult. Science 1998;282:2095-2098

    Google Scholar 

  17. Wakayama T, Perry ACF, Zuccotti M, Johnson KR, Yanagimachi R: Full-term developement of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 1998;394:369-374

    Google Scholar 

  18. Dominko T, Mitalipova M, Haley B, Beyhan Z, Memili E, McKusick B, First NL: Bovine oocyte cytoplasm supports development of embryos produced by nuclear transfer of somatic cell nuclei from various mammalian species. Bio Reprod 1999;60:1496-1502

    Google Scholar 

  19. Kubota C, Yamakuchi H, Todoroki J, Mizoshita K, Tabara N, Barber M, Yang X: Six cloned calves produced from adult fibroblast cells after long-term culture. PNAS 2000;97(3):990-995

    Google Scholar 

  20. Slijepcevic P: Telomeres and mechanisms of Robertsonian fusion. Chromosoma 1998;107:136-140

    Google Scholar 

  21. VanSteensel B, de Lange T: Control of telomere length by the human telomeric protein TRF1. Nature 1997;385:740-743

    Google Scholar 

  22. Smith S, Giriat I, Schmitt A, DeLange T: Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science 1998;282:1484-1487

    Google Scholar 

  23. Bodnar AG, Ouellette M, Frolkis M, Holt S, Chiu CP, Morin GB, Harley C, Shay JW, Lichtsteiner S, Wright WE: Extension of life-span by introduction of telomerase into normal human cells. Science 1998;279:335-349

    Google Scholar 

  24. Barnes FL, Collas P, King WA, Westhusian M, Shepherd D: Influence of recipient oocyte cell cycle stage on DNA synthesis, nuclear envelope breakdown, chromosome constitution, and development in nuclear transplant bovine embryos. Mol Reprod Dev 1993;36:33-41

    Google Scholar 

  25. Zakhartchenko V, Stojkovic M, Brem G, Wolf E, Karyoplast-cytoplast volume ratio in bovine nuclear transfer embryos: Effect on the developmental potential. Mol Reprod Dev 1997;48:332-338

    Google Scholar 

  26. Chastant S, Christians E, Campion E, Renard J-P: Quantitative control of gene expression by nucleoplasmic interactions in early mouse embryos: Consequence for reprogrammation by nuclear transfer. Mol Reprod Dev 1996;44:423-432

    Google Scholar 

  27. Fulka J Jr., First NL, Moor RM: Nuclear transplantation in mammals: Remodelling of transplanted nuclei under the influence of maturation promoting factor. Bioessays 1996;18:835-840

    Google Scholar 

  28. Campbell KHS, Loi P, Otaegui P, Wilmut I: Cell cycle coordination in embryo cloning by nuclear transfer. Rev Reprod 1996;1:40-46

    Google Scholar 

  29. Jones MJ, First NL: Expression of cell cycle control protein CDC25 in cleavage stage bovine embryos. Zygote 1995;3:133-139

    Google Scholar 

  30. Liu I, Dai Y, Moore RM: Nuclear transfer in sheep embryos: The effect of cell-cycle coordination between nucleus and cytoplasm and the use of in vitro matured oocytes. Mol Reprod Dev 1997;47:255-264

    Google Scholar 

  31. Zakhartchenko V, Durcova-Hills G, Stojkovic M, Schernthaner W, Prelle K, Steinborn R, Müller M, Brem G, Wolf E: Effects of serum starvation and recloning on the efficiency of nuclear transfer using bovine fetal fibroblasts. J Reprod Fertil 1999;115:325-331

    Google Scholar 

  32. Zhang Y, Li Y: Nuclear-cytoplasmic interaction and development of goat embryos reconstructed by nuclear transplantation: Production of goats by serially cloning embryos. Biol Reprod 1998;58:266-269

    Google Scholar 

  33. DiBerardino MA: Genomic potential of differentiated cells analyzed by nuclear transplantation. Am Zoo 1987;27:623-644

    Google Scholar 

  34. Steinborn R, Schinogl P, Zakhartchenko V, Achmann R, Schernthaner W, Stojkovic M, Wolf E, Muller M, Brem G: Mitochondrial DNA heteroplasmy in cloned cattle produced fetal and adult cell cloning. Nat Genet 2000;25(3):255-257

    Google Scholar 

  35. Evans MJ, Gurer C, Loike JD, Wilmut I, Schnieke AE, Schon EA: Mitochondrial DNA genotypes in nuclear transfer-derived cloned sheep. Nat Genet 1999;23:90-93

    Google Scholar 

  36. Sutovsky P, Moreno RD, Ramalho-Santos J, Dominko T, Simerly C, Schatten G: Ubiquitin tag for sperm mitochondria. Nature 1999;402:371-372

    Google Scholar 

  37. Leese HJ, Donnay I, Thompson JG: Human assisted conception: A cautionary tale. Lessons from domestic animals. Hum Reprod 1998;13(S4):184-202

    Google Scholar 

  38. Hyttel P, Viuff D, Laurincik J, Schmidt M, Thomsen PD, Avery B, Callesen H, Rath D, Niemann H, Rosenkranz C, Schellander K, Ochs RL, Greve T: Risks of in-vitro production of cattle and swine embryos: Aberrations in chromosome numbers, ribosomal RNA gene activation and perinatal physiology. Hum Reprod 2000;15(suppl 5):87-97

    Google Scholar 

  39. Behboodi E, Anderson GB, BonDurant RH, Cargil SL, Kreuscher BR, Medrano JF, Murray JD: Birth of large calves that developed from in vitro-derived bovine embryos. Theriogenology 1995;44:227-232

    Google Scholar 

  40. Young LE, Sinclair KD, Wilmut I: Large offspring syndrome in cattle and sheep. Rev Reprod 1998;3:155-163

    Google Scholar 

  41. Farin PW, Farin CE: Transfer of bovine embryos produced in vivo or in vitro: Survival and fetal development. Biol Reprod 1995;43:210-218

    Google Scholar 

  42. Walker SK, Hartwich KM, Seamark RF: The production of unusually large offspring following embryo manipulation: Concepts and challenges. Theriogenology 1996;45:111-120

    Google Scholar 

  43. Brown BW, Radziewic T: In vitro production of sheep embryos and growth rates of resultant lambs. InProceedings of the International Congress on Animal Reproduction, Sydney, 1996, vol. 3, P22-16

    Google Scholar 

  44. Thompson JG, Gardner DK, Pugh PA, McMillan WH, Tervit HR: Lamb birth weight is affected by culture system utilized during in vitro pre-elongation development of bovine embryos. Biol Reprod 1995;53:1385-1391

    Google Scholar 

  45. VanLangendonckt A, Donnay I, Schuurbiers N, Auquier P, Carolan C, Massip A, Dessy F: Developmental kinetics of bovine embryos in synthetic oviduct fluid medium: Effects of fetal calf serum supplementation. J Reprod Fertil 1997;109:87-93

    Google Scholar 

  46. Gardner DK, Lane M, Spitzer A, Batt P: Enhanced rates of cleavage and development for sheep zygotes cultured to the blastocyst stage in vitro in the absence of serum and somatic cells: Amino acids, vitamins, and culturing embryos in groups stimulate development. Biol Reprod 1994;50:390-400

    Google Scholar 

  47. Bonduelle M, Camus M, DeVos A, Staessen C, Tournaye H, Van Assche E, Verheyen G, Devroey P, Liebaers I, Van Steirteghem A: Seven years of intracytoplasmic sperm injection and follow-up of 1987 subsequent children. Hum Reprod 1999;14(S 1):243-264

    Google Scholar 

  48. Kleemann DO, Walker SK, Seamark RF: Enhanced fetal growth in sheep administered progesterone during the first three days of pregnancy. J Reprod Fertil 1994;102:411-417

    Google Scholar 

  49. Wilson JM, Williams JD, Bondioli KR: Comparison of birth weight and growth characteristics of bovine calves produced by nuclear transfer (cloning), embryo transfer and natural mating. Anim Reprod Sci 1995;38:73-83

    Google Scholar 

  50. Kruip ThAM, denDaas JHG: In vitro produced and cloned embryos: Effects on pregnancy, parturition, and offspring. Theriogenology 1997;47:43-52

    Google Scholar 

  51. Young LE, Fairburn HR: Improving the safety of embryo technologies: Possible role of genomic imprinting. Theriogenology 2000;53:627-648

    Google Scholar 

  52. Eggenschwiler J, Ludwig T, Fisher P, Leighton PA, Tilghman SM, Efstratiadis A: Mouse mutant embryos overexpressing IGF-II exhibit phenotypic features of the Beckwith-Wiedemann and Simpson-Golabi-Behmel syndromes. Genes Dev 1997;11:3128-3142

    Google Scholar 

  53. Young LE, Fernandes K, McEvoy TG, Butterwith SC, Gutierrez CG, Carolan C, Broadbent PJ, Robinson JJ, Wilmut I, Sinclair KD: Epigenic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet 2001;27:153-154

    Google Scholar 

  54. Wang ZQ, Fung MR, Barlow DP, Wagner EF: Regulation of embryonic growth and lysosomal targeting by imprinted Igf2/Mpr gene. Nature 1994;372:464-467

    Google Scholar 

  55. Renard JP, Chastant S, Chesne P, Richard C, Marchal J, Cordonnier N, Chavatte P, Vignon X: Lymphoid hypoplasia and somatic cloning. Lancet 1999;353:1489-1491

    Google Scholar 

  56. Gardner DK: Development of serum-free media for the culture and transfer of human blastocysts. Hum Reprod 1998;13:218-225

    Google Scholar 

  57. Gardner DK: Changes in requirements und utilization of nutrients during mammalian preimplantation embryo development and their significance in embryo culture. Theriogenology 1998;49:83-102

    Google Scholar 

  58. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM: Embryonic stem cell lines derived from human blastocysts. Science 1998;282:1145-1147

    Google Scholar 

  59. Illmensee K, Mintz B: Totipotency and normal differentiation of single teratocarcinoma cells cloned by injection into blastocysts. Proc Nat Acad Sci 1976;73:549-553

    Google Scholar 

  60. Illmensee K, Stevens LC: Teratomas and chimeras. Sci Am 1979;240:86-98

    Google Scholar 

  61. Modlinski JA, Gerhäuser D, Lioi B, Winking H, Illmensee K: Nuclear transfer from teratocarcinoma cells intomouseoocytes and eggs. Development 1990;108:337-348

    Google Scholar 

  62. Thomson JA, Kalishman J, Golos ThG, Durnig M, Harris CP, Becker RA, Hearn JP: Isolation of a primate embryonic stem cell line. Proc Natl Acad Sci 1995;92:7844-7848

    Google Scholar 

  63. Thomson JA, Marshall VS, Trojanowski JQ: Neural differentiation of rhesus embryonic stem cells. APMIS 1998;106(1):149-156

    Google Scholar 

  64. Evans MJ, Kaufmann MH: Establishment in culture of pluripotent cells from mouse embryos. Nature 1981;292:154-156

    Google Scholar 

  65. Fuchs E, Serge JA: Stem cells: A new lease on life. Cell 2000; 111:143-155

    Google Scholar 

  66. Asahara T, Kalka C, Isner JM: Millenium Review: Stem cell therapy and gene transfer for regeneration. Gene Ther 2000;7:451-457

    Google Scholar 

  67. Edwards BE, Gearhart JD, Wallach EE: The human pluripotent stem cell: Impact on medicine and society. Fertil Steril 2000;74(1):1-7

    Google Scholar 

  68. Handyside AH, Kontogianni EH, Hardy EH, Winston RM: Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 1990;344:768-770

    Google Scholar 

  69. Verlinsky Y, Ginsberg N, Lifchez A, Moise J, Strom CM: Analysis of the first polar body: Preconception genetic diagnosis. Hum Reprod 1990;5:826-829

    Google Scholar 

  70. Verlinsky Y, Kuliev AM: An Atlas of Preimplantation Genetic Diagnosis. New York, The Parthenon Publication Group, 2000

    Google Scholar 

  71. Veiga A, Sandalinas M, Benkhalifa M, Boada M, Carrera M, Santalo J, Barri PN, Menezo Y: Laser blastocyst biopsy for preimplantation genetic diagnosis in the human. Zygote 1997;5:351-354

    Google Scholar 

  72. Staessen C, Van Assche E, Joris H: Preimplantation diagnosis by fluorescent in-situ hybridization in embryos from 47,XXY of 47 XXX patients. J Assist Reprod Genet 1997;14:468

    Google Scholar 

  73. Verlinsky Y, Cieslak J, Ivakhnenko V, Lifchez A, Strom C, Kuliev A: Birth of healthy children after preimplantation diagnosis of common aneuploidies by polar body fluorescent in-situ hybridization analysis. Fertil Steril 1996;66:126-129

    Google Scholar 

  74. Handyside A, Scriven PN, Ogilvie C: The future of preimplantation genetic diagnosis. Hum Reprod 1998;13:249-255

    Google Scholar 

  75. Stice SL, Robl JM, Ponce de Leon FA, Jerry J, Golueke PG, Cibelli JB, Kane JJ: Cloning: new breakthroughs leading to commercial opportunities. Theriogenology 1998;49:129-138

    Google Scholar 

  76. Hammer R, Pursel VG, Rexroad CE Jr, Wall RJ, Bolt DJ, Ebert KM, Palmiter RD, Brinster RL: Production of transgenic rabbits, sheep, and pigs by microinjection. Nature 1985;315:680-683

    Google Scholar 

  77. Brem G, Brenig B, Goodman H, Selden RC, Graf F, Kruff B, Springmann K, Hondele J, Meyer J, Winnacker EL, Kräusslich H: Production of transgenic mice, rabbits, and pigs by microinjection into pronuclei. Zuchthygiene 1985;20:251-252

    Google Scholar 

  78. Chan AW, Homan EJ, Ballou LU, Burns JC, Bremel RD: Transgenic cattle produced by reverse-transcribed gene transfer in oocytes. Proc Natl Acad Sci USA 1998;95:14028-14033

    Google Scholar 

  79. Chan AWS, Chong KY, Martinivich C, Simerly C, Schatten G: Transgenic monkeys produced by retroviral gene transfer into mature oocytes. Science 2001;291:309-312

    Google Scholar 

  80. Spadafora C: Sperm cells and foreign DNA: A controversioal relation. Bioessays 1998;20:955-964

    Google Scholar 

  81. Lavitrano M, Stoppacciaro A, Bacci ML, Forni M, Fioretti D, Pucci L, DiStefano C, Lazzerschi D, Rughetti A, Ceretta S, Zannoni A, Rahimi H, Moioli B, Rossi M, Nuti M, Seren E, Alfani D, Cortesini R, Frati L: Human decay accelerating factor transgenic pigs for xenotransplantation obtained by sperm-mediated gene transfer. Transplant Proc 1999;31:972-974

    Google Scholar 

  82. Zuelke KA: Trangenic modification of cow milk for value added processing. Reprod Fertil Dev 1998;10:671-676

    Google Scholar 

  83. Wolf E, Schernthaner W, Zakhartchenko V, Prelle K, Stojkovic M, Brem G: Transgenic technology in farm animals-progress and perspectives. Exp Physiol 2000;85(6):615-625

    Google Scholar 

  84. Tanos V, Schenker JG: Is human cloning justified? J Assist Reprod Genet 1998;15:1-9

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gynaecology and Obstetrics, University of Innsbruck, Anichstrasse 35, A-6020, Innsbruck, Austria

    Karl Illmensee

Authors
  1. Karl Illmensee
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Illmensee, K. A Seminar on Human Cloning: Cloning in Reproductive Medicine. J Assist Reprod Genet 18, 451–467 (2001). https://doi.org/10.1023/A:1016642906286

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1016642906286

Search

Navigation