Skip to main content
SpringerLink
Log in

Comparison of potency between histone deacetylase inhibitors trichostatin A and valproic acid on enhancing in vitro development of porcine somatic cell nuclear transfer embryos

  • Report
  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

Epigenetic modification influences reprogramming and subsequent development of somatic cell nuclear transfer (SCNT) embryos. Such modification includes an increase in histone acetylation. Histone deacetylase inhibitors (HDACi), such as trichostatin A (TSA) and valproic acid (VPA), have been known to maintain a high cellular level of histone acetylation. Hence, treatment of nuclear transfer embryos with HDACi may increase the efficiency of cloning. The present study attempted direct comparison of TSA and VPA with regard to the potency of enhancement of in vitro development in porcine SCNT embryos. Reconstructed oocytes using fetal fibroblasts were cultured in PZM-3 containing no HDACi (control), 5 mM VPA, or 50 nM TSA for 24 h, and another 5 d thereafter without HDACi. The frequency of blastocyst formation was significantly higher (P < 0.05) in embryos treated with VPA than the frequencies with TSA and without HDACi (125/306, 40.8% vs. 94/313, 30.2% vs. 80/329, 23.4%). In addition, VPA treatment significantly increased (P < 0.05) the number of inner cell mass (ICM) cells compared with the control (15.6 ± 1.7 vs. 10.8 ± 2.6), whereas no differences were observed between the TSA treatment and control groups (12.9 ± 3.0 vs. 10.8 ± 2.6). The present study demonstrates that VPA enhances in vitro development of porcine SCNT embryos, particularly by an increase in blastocyst formation and in the number of ICM cells, suggesting that VPA may be more potent than TSA in supporting developmental competence of cloned embryos.

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

Figure 1.
Figure 2.

Similar content being viewed by others

References

  • Beebe L. F. S; McIlfatrick S. J; Nottle M. B. Cytochalasin B and trichostatin A treatment postactivation improves in vitro development of porcine somatic cell nuclear transfer embryos. Cloning Stem Cells 11:477–482; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Betthauser J.; Forsberg E.; Augenstein M.; Childs L.; Eilertsen K.; Enos J.; Forsythe T.; Golueke P.; Jurgella G.; Koppang R.; Lesmeister T.; Mallon K.; Mell G.; Misica P.; Pace M.; Pfister-Genskow M.; Strelchenko N.; Voelker G.; Watt S.; Thompson S.; Bishop M. Production of cloned piglets from in vitro systems. Nat Biotechnol 18:1055–1059; 2000.

    Article  PubMed  CAS  Google Scholar 

  • Cervera R. P.; Martí-Gutiérrez N.; Escorihuela E.; Moreno R.; Stojkovic M. Trichostatin A affects histone acetylation and gene expression in porcine somatic cell nucleus transfer embryos. Theriogenology 72:1097–1110; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Colman A.; Dreesen O. Induced pluripotent stem cells and the stability of the differentiated state. EMBO Rep 10:714–721; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Dai Y.; Vaught T. D.; Boone J.; Chen S. H.; Phelps C. J.; Ball S.; Monahan J. A.; Jobst P. M.; McCreath K. J.; Lamborn A. E.; Cowell-Lucero J. L.; Wells K. D.; Colman A.; Polejaeva I. A.; Ayares D. L. Targeted disruption of the alpha1,3-galactosyltransferase gene in cloned pigs. Nat Biotechnol 20:251–255; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Dean W.; Santos F.; Stojkovic M.; Zakhartchenko V.; Walter J.; Wolf E.; Reik W. Conservation of methylation reprogramming in mammalian development: aberrant reprogramming in cloned embryos. Proc Natl Acad Sci USA 98:13734–13738; 2001.

    Article  PubMed  CAS  Google Scholar 

  • Feldman N.; Gerson A.; Fang J.; Li E.; Zhang Y.; Shinkai Y.; Cedar H.; Bergman Y. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat Cell Biol 8:188–194; 2006.

    Article  PubMed  CAS  Google Scholar 

  • Göttlicher M.; Minucci S.; Zhu P.; Krämer O. H.; Schimpf A.; Giavara S.; Sleeman J. P.; Lo Coco F.; Nervi C.; Pelicci P. G.; Heinzel T. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J 20:6969–6978; 2001.

    Article  PubMed  Google Scholar 

  • Grunstein M. Histone acetylation in chromatin structure and transcription. Nature 389:349–352; 1997.

    Article  PubMed  CAS  Google Scholar 

  • Huangfu D.; Maehr R.; Guo W.; Eijkelenboom A.; Snitow M.; Chen A. E.; Melton D. A. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 26:795–797; 2008a.

    Article  PubMed  CAS  Google Scholar 

  • Huangfu D.; Osafune K.; Maehr R.; Guo W.; Eijkelenboom A.; Chen S.; Muhlestein W.; Melton D. A. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol 26:1269–1275; 2008b.

    Article  PubMed  CAS  Google Scholar 

  • Jeanisch R.; Eggan K.; Humpherys D.; Rideout W.; Hochedlinger K. Nuclear cloning, stem cells, and genomic reprogramming. Cloning Stem Cells 4:389–396; 2002.

    Article  PubMed  Google Scholar 

  • Kang Y. K.; Koo D. B.; Park J. S.; Choi Y. H.; Kim H. N.; Chang W. K.; Lee K. K.; Han Y. M. Aberrant methylation of donor genome in cloned bovine embryos. Nat Genet 28:173–177; 2001.

    Article  PubMed  CAS  Google Scholar 

  • Kang Y. K.; Yeo S; Kim S. H.; Koo D. B.; Park J. S.; Wee G.; Han J. S.; Oh K. B.; Lee K. K.; Han Y. M. Precise recapitulation of methylation change in early cloned embryos. Mol Reprod Dev 66:32–37; 2003.

    Article  PubMed  CAS  Google Scholar 

  • Kastenberg Z. J.; Odorico J. S. Alternative sources of pluripotency: science, ethics, and stem cells. Transplant Rev (Orlando) 22:215–222; 2008.

    Google Scholar 

  • Kishigami S.; Mizutani E.; Ohta H.; Hikichi T.; Thuan N. V.; Wakayama S.; Bui H. T.; Wakayama T. Significant improvement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer. Biochem Biophys Res Commun 340:183–189; 2006.

    Article  PubMed  CAS  Google Scholar 

  • Lai L.; Kolber-Simonds D.; Park K. W.; Cheong H. T.; Greenstein J. L.; Im G. S.; Samuel M.; Bonk A.; Rieke A.; Day B. N.; Murphy C. N.; Carter D. B.; Hawley R. J.; Prather R. S. Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295:1089–1092; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Lee D. Y.; Hayes J. J.; Pruss D.; Wolffe A. P. A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell 72:73–84; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Li E. Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet 3:662–673; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Li J.; Svarcova O.; Villemoes K.; Kragh P. M.; Schmidt M.; Bøgh I. B.; Zhang Y.; Du Y.; Lin L.; Purup S.; Xue Q.; Bolund L.; Yang H.; Maddox-Hyttel P.; Vajta G. High in vitro development after somatic cell nuclear transfer and trichostatin A treatment of reconstructed porcine embryos. Theriogenology 70:800–808; 2008.

    Article  PubMed  CAS  Google Scholar 

  • Meng Q.; Polgar Z.; Liu J.; Dinnyes A. Live birth of somatic cell-cloned rabbits following trichostatin A treatment and cotransfer of parthenogenetic embryos. Cloning Stem Cells 11:203–208; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Miyoshi K.; Mori H.; Mizobe Y.; Akasaka E.; Ozawa A.; Yoshida M.; Sato M. Valproic acid enhances in vitro development and oct-3/4 expression of miniature pig somatic cell nuclear transfer embryos. Cell Reprogram 12:67–74; 2010.

    PubMed  CAS  Google Scholar 

  • Ohgane J.; Wakayama T.; Senda S.; Yamazaki Y.; Inoue K.; Ogura A.; Marh J.; Tanaka S.; Yanagimachi R.; Shiota K. The Sall3 locus is an epigenetic hotspot of aberrant DNA methylation associated with placentomegaly of cloned mice. Genes Cells 9:253–260; 2004.

    Article  PubMed  CAS  Google Scholar 

  • Onishi A.; Iwamoto M.; Akita T.; Mikawa S.; Takeda K.; Awata T.; Hanada H.; Perry A. C. Pig cloning by microinjection of fetal fibroblast nuclei. Science 289:1188–1190; 2000.

    Article  PubMed  CAS  Google Scholar 

  • Polejaeva I. A.; Chen S. H.; Vaught T. D.; Page R. L.; Mullins J.; Ball S.; Dai Y.; Boone J.; Walker S.; Ayares D. L.; Colman A.; Campbell K. H. S. Cloned pigs produced by nuclear transfer from adult somatic cells. Nature 407:86–90; 2000.

    Article  PubMed  CAS  Google Scholar 

  • Pratt S. L.; Sherrer E. S.; Reeves D. E.; Stice S. L. Factors influencing the commercialisation of cloning in the pork industry. Soc Reprod Fertil Suppl 62:303–315; 2006.

    PubMed  CAS  Google Scholar 

  • Rogers C S.; Hao Y.; Rokhlina T.; Samuel M.; Stoltz D. A.; Li Y.; Petroff E.; Vermeer D. W.; Kabel A. C.; Yan Z.; Spate L.; Wax D.; Murphy C. N.; Rieke A.; Whitworth K.; Linville M. L.; Korte S. W.; Engelhardt J. F.; Welsh M. J.; Prather R. S. Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer. J Clin Invest 118:1571–1577; 2008a.

    Article  PubMed  CAS  Google Scholar 

  • Rogers C. S.; Stoltz D. A.; Meyerholz D. K.; Ostedgaard L. S.; Rokhlina T.; Taft P. J.; Rogan M. P.; Pezzulo A. A.; Karp P. H.; Itani O. A.; Kabel A. C.; Wohlford-Lenane C. L.; Davis G. J.; Hanfland R. A.; Smith T. L.; Samuel M.; Wax D.; Murphy C. N.; Rieke A.; Whitworth K.; Uc A.; Starner T. D.; Brogden K. A.; Shilyansky J.; McCray P. B. Jr.; Zabner J.; Prather R. S.; Welsh M. J. Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 321:1837–1841; 2008b.

    Article  PubMed  CAS  Google Scholar 

  • Rybouchkin A.; Kato Y.; Tsunoda Y. Role of histone acetylation in reprogramming of somatic nuclei following nuclear transfer. Biol Reprod 74:1083–1089; 2006.

    Article  PubMed  CAS  Google Scholar 

  • Santos F.; Zakhartchenko V.; Stojkovic M.; Peters A.; Jenuwein T.; Wolf E.; Reik W.; Dean W. Epigenetic marking correlates with developmental potential in cloned bovine preimplantation embryos. Curr Biol 13:1116–1121; 2003.

    Article  PubMed  CAS  Google Scholar 

  • Svensson K.; Mattsson R.; James T. C.; Wentzel P.; Pilartz M.; MacLaughlin J.; Miller S. J.; Olsson T.; Eriksson U. J.; Ohlsson R. The paternal allele of the H19 gene is progressively silenced during early mouse development: the acetylation status of histones may be involved in the generation of variegated expression patterns. Development 125:61–69; 1998.

    PubMed  CAS  Google Scholar 

  • Thorne A. W.; Kmiciek D.; Mitchelson K.; Sautiere P.; Crane-Robinson C. Patterns of histone acetylation. Eur J Biochem 193:701–713; 1990.

    Article  PubMed  CAS  Google Scholar 

  • Tsuji Y.; Kato Y.; Tsunoda Y. The developmental potential of mouse somatic cell nuclear-transferred oocytes treated with trichostatin A and 5-aza-20-deoxycytidine. Zygote 17:109–115; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Turner B. M. Histone acetylation as an epigenetic determinant of long-term transcriptional competence. Cell Mol Life Sci 54:21–31; 1998.

    Article  PubMed  CAS  Google Scholar 

  • Vajta G.; Zhang Y.; Machaty Z. Somatic cell nuclear transfer in pigs: recent achievements and future possibilities. Reprod Fertil Dev 19:403–423; 2007.

    Article  PubMed  Google Scholar 

  • Yamanaka K.; Sugimura S.; Wakai T.; Kawahara M.; Sato E. Acetylation level of histone H3 in early embryonic stage affects subsequent development of miniature pig somatic cell nuclear transfer embryos. J Reprod Devel 55:638–644; 2009.

    Article  Google Scholar 

  • Yang X.; Smith S. L.; Tian X. C.; Lewin H. A.; Renard J. P.; Wakayama T. Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning. Nat Genet 39:295–302; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Yoshida M.; Kijima M.; Akita M.; Beppu T. Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 265:17174–17179; 1990.

    PubMed  CAS  Google Scholar 

  • Zhang Y.; Li J.; Villemoes K.; Pedersen A. M.; Purup S.; Vajta G. An epigenetic modifier results in improved in vitro blastocyst production after somatic cell nuclear transfer. Cloning Stem Cells 9:357–363; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Zhao J.; Ross J. W.; Hao Y.; Spate L. D.; Walters E. M.; Samuel M. S.; Rieke A.; Murphy C. N.; Prather R. S. Significant improvement in cloning efficiency of an inbred miniature pig by histone deacetylase inhibitor treatment after somatic cell nuclear transfer. Biol Reprod 81:525–530; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Zhu W. G.; Otterson G. A. The interaction of histone deacetylase inhibitors and DNA methyltransferase inhibitors in the treatment of human cancer cells. Curr Med Chem Anticancer Agents 3:187–199; 2003.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by a grant (F104AD010002-08A0401-00220) from the Korea Biotech R&D Group of Next-Generation Growth Engine Project, a grant (R31-2008-000-100069-0) from the World Class University Project, a grant (KRF-2009-0093829) from the Korea Research Foundation, Ministry of Education, Science and Technology, a grant (108080-03-2-SB010) from the Technology Development Program for Agriculture and Forestry, Ministry for Food, Agriculture, Forestry and Fisheries, and grants (20050301-034-410-009-01-00 and 20070301-034-040-009-04-00) from the BioGreen 21 Program, Rural Development Administration, Republic of Korea.

Author information

Authors and Affiliations

  1. Department of Nanobiomedical Science and WCU Research Center for Nanobiomedical Science, Dankook University, San 29 Anseo-dong, Cheonan, Chungnam, 330-714, South Korea

    Young June Kim, Kwang Sung Ahn, Minjeong Kim & Hosup Shim

  2. Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, 330-714, South Korea

    Hosup Shim

Authors
  1. Young June Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kwang Sung Ahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Minjeong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hosup Shim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hosup Shim.

Additional information

Editor: J. Denry Sato

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, Y.J., Ahn, K.S., Kim, M. et al. Comparison of potency between histone deacetylase inhibitors trichostatin A and valproic acid on enhancing in vitro development of porcine somatic cell nuclear transfer embryos. In Vitro Cell.Dev.Biol.-Animal 47, 283–289 (2011). https://doi.org/10.1007/s11626-011-9394-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-011-9394-7

Keywords

Search

Navigation