DOI QR코드

DOI QR Code

The Role of Protein Kinases in Reprogramming and Development of SCNT Embryos

  • Choi, Inchul (Animal Development and Biotechnology Group, School of Biosciences, The University of Nottingham, Sutton Bonington Campus) ;
  • Campbell, Keith H.S. (Animal Development and Biotechnology Group, School of Biosciences, The University of Nottingham, Sutton Bonington Campus)
  • 투고 : 2015.02.25
  • 심사 : 2015.03.21
  • 발행 : 2015.03.31

초록

Successful somatic cell nuclear transfer (SCNT) has been reported across a range of species using a range of recipient cells including enucleated metaphase II (MII) arrested oocytes, enucleated activated MII oocytes, and mitotic zygotes. However, the frequency of development to term varies significantly, not only between different cytoplast recipients but also within what is thought to be a homogenous population of cytoplasts. One of the major differences between cytoplasts is the activities of the cell cycle regulated protein kinases, maturation promoting factor (MPF) and mitogen activated protein kinase (MAPK). Dependent upon their activity, exposure of the donor nucleus to these kinases can have both positive and negative effects on subsequent development. Co-ordination of cell cycle stage of the donor nucleus with the activities of MPF and MAPK in the cytoplast is essential to avoid DNA damage and maintain correct ploidy. However, recent information suggests that these kinases may also effect reprogramming of the somatic nucleus and preimplantation embryo development by other mechanisms. This article will summarise the differences between cytoplast recipients, their effects on development and discuss the potential role/s of MPF and or MAPK in nuclear reprogramming.

키워드

참고문헌

  1. Baguisi A, Behboodi E, Melican DT, Pollock JS, Destrempes MM, Cammuso C, Williams JL, Nims SD, Porter CA, Midura P, Palacios MJ, Ayres SL, Denniston RS, Hayes ML, Ziomek CA, Meade HM, Godke RA, Gavin WG, Overstrom EW and Echelard Y. 1999. Production of goats by somaticcell nuclear transfer. Nat. Biotechnol 17:456-461. https://doi.org/10.1038/8632
  2. Barnes FL, Collas P, Powell R, King WA, Westhusin M and Shepherd D. 1993. Influence of recipient oocyte cell-cycle stage on DNA synthesis, nuclear envelope breakdown, chromosome constitution, and development in nuclear transplant bovine embryos. Molecular Reproduction and Development 36:33-41. https://doi.org/10.1002/mrd.1080360106
  3. Betts DH and King WA. 2001. Genetic regulation of embryo death and senescence. Theriogenology 55:171-191. https://doi.org/10.1016/S0093-691X(00)00453-2
  4. Boiani M, Eckardt S, Scholer HR and McLaughlin KJ. 2002. Oct4 distribution and level in mouse clones: Consequences for pluripotency. Genes Dev. 16:1209-1219. https://doi.org/10.1101/gad.966002
  5. Brison DR and Schultz RM. 1997. Apoptosis during mouse blastocyst formation: Evidence for a role for survival factors including transforming growth factor alpha. Biol. Reprod. 56:1088-96. https://doi.org/10.1095/biolreprod56.5.1088
  6. Brison DR and Schultz RM. 1998. Increased incidence of apoptosis in transforming growth factor alpha-deficient mouse blastocysts. Biol. Reprod. 59:136-144. https://doi.org/10.1095/biolreprod59.1.136
  7. Campbell KH, Loi P, Cappai P and Wilmut I. 1994. Improved development to blastocyst of ovine nuclear transfer embryos reconstructed during the presumptive S-phase of enucleated activated oocytes. Biol. Reprod. 50:1385-1393. https://doi.org/10.1095/biolreprod50.6.1385
  8. Campbell KH, McWhir J, Ritchie WA and Wilmut I. 1996. Sheep cloned by nuclear transfer from a cultured cell line. Nature 380:64-66. https://doi.org/10.1038/380064a0
  9. Campbell KH, Ritchie WA and Wilmut I. 1993. Nuclear-cytoplasmic interactions during the first cell cycle of nuclear transfer reconstructed bovine embryos: Implications for deoxyribonucleic acid replication and development. Biol. Reprod. 49:933-942. https://doi.org/10.1095/biolreprod49.5.933
  10. Chesne P, Adenot PG, Viglietta C, Baratte M, Boulanger L and Renard JP. 2002. Cloned rabbits produced by nuclear transfer from adult somatic cells. Nature Biotechnology 20:366-369. https://doi.org/10.1038/nbt0402-366
  11. Cheung P, Tanner KG, Cheung WL, Sassong-Corsi P, Denu JM and Allis CD. 2000. Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation. Molecular Cell 5:905-915. https://doi.org/10.1016/S1097-2765(00)80256-7
  12. Choi I and Campbell KHS. 2010. Treatment of ovine oocytes with caffeine increases the accessibility of DNase I to the donor chromatin and reduces apoptosis in somatic cell nuclear transfer embryos. Reproduction, Fertility and Development 22:1000-1014. https://doi.org/10.1071/RD09144
  13. Choi I, Lee J-H, Fisher P and Campbell KHS. 2010. Caffeine treatment of ovine cytoplasts regulates gene expression and foetal development of embryos produced by somatic cell nuclear transfer. Molecular Reproduction and Development 77:876-887. https://doi.org/10.1002/mrd.21230
  14. Choi T, Aoki F, Mori M, Yamashita M, Nagahama Y and Kohmoto K. 1991. Activation of p34cdc2 protein kinase activity in meiotic and mitotic cell cycles in mouse oocytes and embryos. Development 113:789-795.
  15. Christians ES, Zhou Q, Renard J and Benjamin IJ. 2003. Heat shock proteins in mammalian development. Seminars in Cell & Developmental Biology 14:283-290. https://doi.org/10.1016/j.semcdb.2003.09.021
  16. Chung YG, Ratnam S, Chaillet JR and Latham KE. 2003. Abnormal regulation of DNA methyltransferase expression in cloned mouse embryos. Biology of Reproduction 69:146-153. https://doi.org/10.1095/biolreprod.102.014076
  17. Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Blackwell C, Ponce DL and Robl JM. 1998. Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science 280:1256-1258. https://doi.org/10.1126/science.280.5367.1256
  18. Collas P, Le Guellec K and Taskaan K. 1999. The a-Kinasea "anchoring protein Akap95 Is a multivalent protein with a key role in chromatin condensation at mitosis. The Journal of Cell Biology 147:1167-1180. https://doi.org/10.1083/jcb.147.6.1167
  19. Collas P, Pinto-Correia C, Ponce DL and Robl JM. 1992. Effect of donor cell cycle stage on chromatin and spindle morphology in nuclear transplant rabbit embryos. Biology of Reproduction 46:501-511. https://doi.org/10.1095/biolreprod46.3.501
  20. Collas P and Robl JM. 1991. Relationship between nuclear remodeling and development in nuclear transplant rabbit embryos. Biology of Reproduction 45:455-465. https://doi.org/10.1095/biolreprod45.3.455
  21. Constant F, Guillomot M, Heyman Y, Vignon X, Laigre P, Servely JL, Renard JP and Chavatte-Palmer P. 2006. Large offspring or large placenta syndrome? morphometric analysis of late gestation bovine placentomes from somatic nuclear transfer pregnancies complicated by Hydrallantois. Biology of Reproduction, 75:122-130. https://doi.org/10.1095/biolreprod.106.051581
  22. De La Fuente R. 2006. Chromatin modifications in the germinal vesicle (GV) of mammalian oocytes. Developmental Biology 292:1-12. https://doi.org/10.1016/j.ydbio.2006.01.008
  23. Dedieu T, Gall L, Ctozet N, Sevellec C and Ruffini S. 1996. Mitogen-activated protein kinase activity during goat oocyte maturation and the acquisition of meiotic competence. Molecular Reproduction and Development 45:351-358. https://doi.org/10.1002/(SICI)1098-2795(199611)45:3<351::AID-MRD12>3.0.CO;2-1
  24. Egli D, Rosains J, Birkhoff G and Eggan K. 2007. Developmental reprogramming after chromosome transfer into mitotic mouse zygotes. Nature 447:679-685. https://doi.org/10.1038/nature05879
  25. Egli D, Sandler VM, Shinohara ML, Cantor H and Eggan K. 2009. Reprogramming after chromosome transfer into mouse blastomeres. Curr. Biol. 19:1403-1409. https://doi.org/10.1016/j.cub.2009.06.065
  26. Enright BP, Kubota C, Yang X and Tian XC. 2003. Epigenetic characteristics and development of embryos cloned from donor cells treated by trichostatin A or 5-aza-$2a^2$-deoxycytidine. Biology of Reproduction 69:896-901. https://doi.org/10.1095/biolreprod.103.017954
  27. Fahrudin M, Otoi T, Karga NW, Mori M, Murakami M and Suzuki T. 2002. Analysis of DNA fragmentation in bovine somatic nuclear transfer embryos using TUNEL. Reproduction 124:813-819. https://doi.org/10.1530/rep.0.1240813
  28. Fan H-Y and Sun Q-Y. 2004. Involvement of mitogen-activated protein kinase cascade during oocyte maturation and fertilization in mammals. Biology of Reproduction 70:535-547. https://doi.org/10.1095/biolreprod.103.022830
  29. Fissore RA, He CL and Vande WGF. 1996. Potential role of mitogen-activated protein kinase during meiosis resumption in bovine oocytes. Biology of Reproduction 55:1261-1270. https://doi.org/10.1095/biolreprod55.6.1261
  30. Folch J, Cocero MJ, Chesne P, Alabart JL, Dominguez V, Cognie Y, Roche A, Fernandez-Arias A, Marti JI, Sanchez P, Echegoyen E, Beckers JF, Bonastre AS and Vignon X. 2009. First birth of an animal from an extinct subspecies (Capra pyrenaica pyrenaica) by cloning. Theriogenology 71:1026-1034. https://doi.org/10.1016/j.theriogenology.2008.11.005
  31. Galasinski SC, Resing KA, Goodrich JA and Ahn NG. 2002. Phosphatase inhibition leads to histone deacetylases 1 and 2 phosphorylation and disruption of corepressor interactions. Journal of Biological Chemistry 277:19618-19626. https://doi.org/10.1074/jbc.M201174200
  32. Galli C, Lacutina I, Crotti G, Colleoni S, Turini P, Ponderato N, Duchi R and Lazzari G. 2003. Pregnancy: A cloned horse born to its dam twin. Nature 424:635.
  33. Gao S, Chung YG, Willians JW, Riley J, Moley K and Latham KE. 2003. Somatic cell-like features of cloned mouse embryos prepared with cultured myoblast nuclei. Biology of Reproduction 69:48-56. https://doi.org/10.1095/biolreprod.102.014522
  34. Gebauer F and Richter JD. 1997. Synthesis and function of Mos: The control switch of vertebrate oocyte meiosis. Bioessays 19:23-28. https://doi.org/10.1002/bies.950190106
  35. Gjarret JO, Knijn HM, Dieleman SJ, Avery B, Larsson L-I and Maddox-Hyttel P. 2003. Chronology of apoptosis in bovine embryos produced in vivo and in vitro. Biology of Reproduction 69:1193-1200. https://doi.org/10.1095/biolreprod.102.013243
  36. Goudet G, Belin FB, Zard J and G Rard N. 1998. Maturationpromoting factor (MPF) and mitogen activated protein kinase (MAPK) expression in relation to oocyte competence for in-vitro maturation in the mare. Molecular Human Reproduction 4:563-570. https://doi.org/10.1093/molehr/4.6.563
  37. Gregory RI, O'neill LP, Randall TE, Foutnier C, Khosla S, Turner BM and Feil R. 2002. Inhibition of histone deacetylases alters allelic chromatin conformation at the imprinted U2af1-rs1 locus in mouse embryonic stem cells. Journal of Biological Chemistry 277:11728-11734. https://doi.org/10.1074/jbc.M105775200
  38. Gregory RI, Randall TE, Johnson CA, Khosla S, Hatada I, O'neill LP, Turner BM and Feil R. 2001. DNA methylation is linked to deacetylation of histone H3, but not H4, on the imprinted genes snrpn and U2af1-rs1. Mol. Cell. Biol. 21:5426-5436. https://doi.org/10.1128/MCB.21.16.5426-5436.2001
  39. Gross A, McDonnell JM and Korsmeyer SJ. 1999. BCL-2 family members and the mitochondria in apoptosis. Genes & Development 13:1899-1911. https://doi.org/10.1101/gad.13.15.1899
  40. Hao Y, Lai L, Mao J, Im G-S, Bonk A and Prather RS. 2003. Apoptosis and in vitro development of preimplantation porcine embryos derived in vitro or by nuclear transfer. Biology of Reproduction 69:501-507. https://doi.org/10.1095/biolreprod.103.016170
  41. Hirabayashi M, Kato M, Ishikawa A and Hochi S. 2003. Factors influencing chromosome condensation and development of cloned rat embryos. Cloning and Stem Cells 5:35-42. https://doi.org/10.1089/153623003321512148
  42. Huot J, Lambert H, Lavoie JN, Guimond A, Houle F and Landry J. 1995. Characterization of 45-kDa/54-kDa HSP27 kinase, a stress-sensitive kinase which may activate the phosphorylation-dependent protective function of mammalian 27-kDa heat-shock protein HSP27. Eur. J. Biochem. 227:416-27. https://doi.org/10.1111/j.1432-1033.1995.tb20404.x
  43. Iager AE, Ragina NP, Ross PJ, Beyhan Z, Cunniff K, Rodricuez RM and Cibelli JB. 2008. Trichostatin a improves histone acetylation in bovine somatic cell nuclear transfer early embryos. Cloning and Stem Cells 10:371-380. https://doi.org/10.1089/clo.2007.0002
  44. Kang E, Wu G, Ma H, Li Y, Tippner-Hedges R, Tachibana M, Sparman M, Wolf DP, Scholer HR and Mitalipov S. 2014. Nuclear reprogramming by interphase cytoplasm of two-cell mouse embryos. Nature 509:101-104. https://doi.org/10.1038/nature13134
  45. Knijin HM, Gjarret JO, Vos PLAM, Hendriksen PJM, Van Der Weijden BC, Maddox-Hyttel P and Dieleman SJ. 2003. Consequences of in vivo development and subsequent culture on apoptosis, cell number and blastocyst formation in bovine embryos. Biology of Reproduction 69:1371-1378. https://doi.org/10.1095/biolreprod.103.017251
  46. Lanza RP, Cibelli JB, Diaz F, Moraes CT, Farin PW, Farin CE, Hammer CJ, West MD and Damiani P. 2000. Cloning of an endangered species (Bos gaurus) using interspecies nuclear transfer. Cloning 2:79-90. https://doi.org/10.1089/152045500436104
  47. Lavoie JN, Gingras-Breton G, Tanguay RM and Landry J. 1993. Induction of Chinese hamster HSP27 gene expression in mouse cells confers resistance to heat shock. HSP27 stabilization of the microfilament organization. J. Biol. Chem. 268L3420-3429.
  48. Lavoie JN, Lambert H, Hickey E, Weber LA and Landry J. 1995. Modulation of cellular thermoresistance and actin fila ment stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27. Mol. Cell Biol. 15:505-516. https://doi.org/10.1128/MCB.15.1.505
  49. Lee BC, Kim MK, Jang G, Oh HJ, Yuda F, Kim HJ, Shamim MH, Kim JJ, Kang SK, Schatten G and Hwang WS. 2005. Dogs cloned from adult somatic cells. Nature 436:641. https://doi.org/10.1038/436641a
  50. Lee ER, McCool KW, Murdoch FE and Fritsch MK. 2006. Dynamic changes in histone H3 phosphoacetylation during early embryonic stem cell differentiation are directly mediated by mitogen- and stress-activated protein kinase 1 via activation of MAPK pathways. Journal of Biological Chemistry 281:21162-21172. https://doi.org/10.1074/jbc.M602734200
  51. Lee J-H and Campbell KHS. 2008. Caffeine treatment prevents age-related changes in ovine oocytes and increases cell numbers in blastocysts produced by somatic cell nuclear transfer. Cloning and Stem Cells 10:381-390. https://doi.org/10.1089/clo.2007.0091
  52. Lee J-H, Peters A, Fisher P, Bowles EJ, ST. John JC and Campbell KHS. 2010. Generation of mtDNA homoplasmic cloned lambs. Cellular Reprogramming 12:347-355. https://doi.org/10.1089/cell.2009.0096
  53. Lee JH and Campbell KH. 2006. Effects of enucleation and caffeine on maturation-promoting factor (MPF) and mitogenactivated protein kinase (MAPK) activities in ovine oocytes used as recipient cytoplasts for nuclear transfer. Biol. Reprod. 74:691-698. https://doi.org/10.1095/biolreprod.105.043885
  54. Li X, Kato Y, Tsuji Y and Tsunoda Y. 2008. The effects of trichostatin A on mRNA expression of chromatin structure-, DNA methylation-, and development-related genes in cloned mouse blastocysts. Cloning and Stem Cells 10:133-142. https://doi.org/10.1089/clo.2007.0066
  55. Li Z, Sun X, Chen J, Liu X, Wisely SM, Zhou Q, Renard JP, Leno GH and Engerlardt JF. 2006. Cloned ferrets produced by somatic cell nuclear transfer. Dev. Biol. 293:439-448. https://doi.org/10.1016/j.ydbio.2006.02.016
  56. Liu S-Z, Yao L-J, Jiang M-X, Lei Z-L, Zhang L-S, Zhang Y-L, Sun Q-Y, Zheng Y-L, Sing X-F and Chen D-Y. 2005. Apoptosis in rabbit embryos produced by fertilization or nuclear transfer with fibroblasts and cumulus cells. Reproduction 130:359-366. https://doi.org/10.1530/rep.1.00658
  57. Loi P, Ptak G, Barboni B, Fulka J JR, Cappai P and Cliton M. 2001. Genetic rescue of an endangered mammal by crossspecies nuclear transfer using post-mortem somatic cells. Nat. Biotechnol. 19:962-964. https://doi.org/10.1038/nbt1001-962
  58. Mart Nez-Balb SMA, Dey A, Rabindran SK, Ozato K and Wu C. 1995. Displacement of sequence-specific transcription factors from mitotic chromatin. Cell 83:29-38. https://doi.org/10.1016/0092-8674(95)90231-7
  59. McGrath J and Solter D. 1983. Nuclear transplantation in the mouse embryo by microsurgery and cell fusion. Science 220:1300-1302. https://doi.org/10.1126/science.6857250
  60. McGrath J and Solter D. 1984. Inability of mouse blastomere nuclei transferred to enucleated zygotes to support development in vitro. Science 226:1317-1319. https://doi.org/10.1126/science.6542249
  61. Oh HJ, Kim MK, Jang G, Kim HJ, Hong SG, Park JE, Park K, Park C, Sohn SH, Kim DY, Shin NS and Lee BC. 2008. Cloning endangered gray wolves (Canis lupus) from somatic cells collected postmortem. Theriogenology 70:638-647. https://doi.org/10.1016/j.theriogenology.2008.04.032
  62. Oh JS, Susor A and Conti M. 2011. Protein tyrosine kinase wee1B is essential for metaphase II exit in mouse oocytes. Science 332:462-465. https://doi.org/10.1126/science.1199211
  63. Ono Y, Shinozawa N, Ito M and Kono T. 2001. Cloned mice from fetal fibroblast cells arrested at metaphase by a serial nuclear transfer. Biology of Reproduction 64:44-50. https://doi.org/10.1095/biolreprod64.1.44
  64. Pfister-Genskow M, Myers C, Childs LA, Lacson JC, Patterson T, Betthauset JM, Goueleke PJ, Koppang RW, Lange G and Fisher P. 2005. Identification of differentially expressed genes in individual bovine preimplantation embryos produced by nuclear transfer: Improper reprogramming of genes required for development. Biol. Reprod. 72:546-555. https://doi.org/10.1095/biolreprod.104.031799
  65. Polejaeva IA, Chen SH, Vaught TD, Page RL, Mullins J, Ball S, Dai Y, Boone J, Walker S, Ayares DL, Colman A and Campbell KHS. 2000. Cloned pigs produced by nuclear transfer from adult somatic cells. Nature 407:86-90. https://doi.org/10.1038/35024082
  66. Prather RS, Sims MM and First NL. 1989. Nuclear transplantation in early pig embryos. Biology of Reproduction 41:414-418. https://doi.org/10.1095/biolreprod41.3.414
  67. Rathbone AJ, Fisher PA, Lee J-H, Craigon J and Campbell KH. 2010. Reprogramming of ovine somatic cells with Xenopus laevis oocyte extract prior to SCNT improves live birth rate. Cellular Reprogramming 12:609-616. https://doi.org/10.1089/cell.2010.0015
  68. Rodriguez-Osorio N, Wang Z, Kasinathan P, Page G, Robl J and Memili E. 2009. Transcriptional reprogramming of gene expression in bovine somatic cell chromatin transfer embryos. BMC Genomics 10:190. https://doi.org/10.1186/1471-2164-10-190
  69. Santos F, Zakhartchenko V, Stojkovic M, Peters A, Jenuwein T, Wolf E, Reik W and Dean W. 2003. Epigenetic marking correlates with developmental potential in cloned bovine preimplantation embryos. Current Biology 13:1116-1121. https://doi.org/10.1016/S0960-9822(03)00419-6
  70. Shin T, Kraemer D, Pryor J, Liu L, Rugila J, Howe L, Buck S, Murphy K, Lyons L and Westhusin M. 2002. Cell biology: A cat cloned by nuclear transplantation. Nature 415:859. https://doi.org/10.1038/nature723
  71. Smith C, Berg D, Beaumont S, Standley NT, Wells DN and Pfeffer PL. 2007. Simultaneous gene quantitation of multiple genes in individual bovine nuclear transfer blastocysts. Reproduction 133:231-242. https://doi.org/10.1530/rep.1.0966
  72. Sinth SL, Everts RE, Tian XC, Du F, Sung LY, Rodriguez-Zas SL, Jeong BS, Renard JP, Lewin HA and Yang X. 2005. Global gene expression profiles reveal significant nuclear reprogramming by the blastocyst stage after cloning. Proceedings of the National Academy of Sciences of the United States of America 102:17582-17587. https://doi.org/10.1073/pnas.0508952102
  73. Sullivan EJ, Kasinathan S, Kasinathan P, Robl JM and Collas P. 2004. Cloned calves from chromatin remodeled in vitro. Biology of Reproduction 70:146-153. https://doi.org/10.1095/biolreprod.103.021220
  74. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K and Yamanaka S. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861-872. https://doi.org/10.1016/j.cell.2007.11.019
  75. Takahashi K and Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676. https://doi.org/10.1016/j.cell.2006.07.024
  76. Tani T, Kato Y and Tsunoda Y. 2001. Direct exposure of chromosomes to nonactivated ovum cytoplasm is effective for bovine somatic cell nucleus reprogramming. Biology of Reproduction 64:324-330. https://doi.org/10.1095/biolreprod64.1.324
  77. Tsuji Y, Kato Y and Tsunoda Y. 2009. The developmental potential of mouse somatic cell nuclear-transferred oocytes treated with trichostatin A and 5-aza-2?-deoxycytidine. Zygote 17:109-115. https://doi.org/10.1017/S0967199408005133
  78. Wakayama S, Cibelli JB and Wakayama T. 2003. Effect of timing of the removal of oocyte chromosomes before or after injection of somatic nucleus on development of NT embryos. Cloning and Stem Cells 5:181-189. https://doi.org/10.1089/153623003769645848
  79. WAakayama T, Perry AC, Zuccotti M, Johnson KR and Yanagimachi R. 1998. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 394:369-374. https://doi.org/10.1038/28615
  80. Wakayama T, Rodriguez I, Perry ACF, Yanagimachi R and Mombaerts P. 1999. Mice cloned from embryonic stem cells. Proceedings of the National Academy of Sciences 96:14984-14989. https://doi.org/10.1073/pnas.96.26.14984
  81. Wakayama T, Tateno H, Mombaerts P and Yamagimachi R. 2000. Nuclear transfer into mouse zygotes. Nat. Genet. 24:108-109. https://doi.org/10.1038/72749
  82. Willadsen SM. 1986. Nuclear transplantation in sheep embryos. Nature 320:63-65. https://doi.org/10.1038/320063a0
  83. Wilmut I, Beaujean N, De Sousa PA, Dinnyes A, King TJ, Paterson LA, Wells DN and Young LE. 2002. Somatic cell nuclear transfer. Nature 419:583-587. https://doi.org/10.1038/nature01079
  84. Wilmut I, Shnieke AE, McWhir J, Kind AJ and Campbell KH. 1997. Viable offspring derived from fetal and adult mammalian cells. Nature 385:810-813. https://doi.org/10.1038/385810a0
  85. Woods GL, White KL, Vanderwall DK, Li GP, Aston KI, Bunch TD, Meerdo LN and Pate BJ. 2003. A mule cloned from fetal cells by nuclear transfer. Science 301:1063. https://doi.org/10.1126/science.1086743
  86. Wrenzycki C, Wells D, Herraann D, Miller A, Oliver J, Tervit R and Niemann H. 2001. Nuclear transfer protocol affects messenger RNA expression patterns in cloned bovine blastocysts. Biology of Reproduction 65:309-317. https://doi.org/10.1095/biolreprod65.1.309
  87. Young LE, Sinclair KD and Wilmut I. 1998. Large offspring syndrome in cattle and sheep. Rev. Reprod. 3:155-163. https://doi.org/10.1530/ror.0.0030155
  88. Yu H-Q, Bou S, Chen D-Y and Sun Q-Y. 2002. Phosphorylation of MAP kinase and p90rsk and its regulation during in vitro maturation of cumulus-enclosed rabbit oocytes. Zygote 10:311-316. https://doi.org/10.1017/S0967199402004045
  89. Zhou Q, Renard JP, Le Friec G, Brochard V, Beaujean N, Cherifi Y, Fraichard A and Cozzi J. 2003. Generation of fertile cloned rats by regulating oocyte activation. Science 302:1179.
  90. Zhou W, Xiang T, Walker S, Farrar V, Hwang E, Findeisen B, Sadeghieh S, Arenivas F, Abruzzese RV and Polefaeva I. 2008. Global gene expression analysis of bovine blastocysts produced by multiple methods. Mol. Reprod. Dev. 75:744-758. https://doi.org/10.1002/mrd.20797