Histone deacetylase inhibitors improve in vitro and in vivo developmental competence of somatic cell nuclear transfer porcine embryos.
Faulty epigenetic reprogramming of somatic nuclei is likely to be a major cause of low success observed in all mammals produced through somatic cell nuclear transfer (SCNT). It has been demonstrated that the developmental competence of SCNT embryos in several species were significantly enhanced via treatment of histone deacetylase inhibitors (HDACi) such as trichostatin A (TSA) to increase histone acetylation. Here we report that 50 nM TSA for 10 h after activation increased the developmental competence of porcine SCNT embryos constructed from Landrace fetal fibroblast cells (FFCs) in vitro and in vivo, but not at higher concentrations. Therefore, we optimized the application of another novel HDACi, Scriptaid, for development of porcine SCNT embryos. We found that treatment with 500 nM Scriptaid significantly enhanced the development SCNT embryos to the blastocyst stage when outbred Landrace FFCs and ear fibroblast cells (EFCs) were used as donors compared to the untreated group. Scriptaid increased the overall cloning efficiency from 0.4% (untreated group) to 1.6% for Landrace FFCs and 0 to 3.7% for Landrace EFCs. Moreover, treatment of SCNT embryos with Scriptaid improved the histone acetylation on Histone H4 at lysine 8 (AcH4K8) in a pattern similar to that of the in vitro fertilized (IVF) embryos.
National Swine Resource and Research Center, University of Missouri, Columbia, Missouri 65211, USA.
Jianguo
J
Zhao
Yanhong
Y
Hao
Jason W
JW
Ross
Lee D
LD
Spate
Eric M
EM
Walters
Melissa S
MS
Samuel
August
A
Rieke
Clifton N
CN
Murphy
Randall S
RS
Prather
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D021461:Animals, Outbred Strains; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019976:Cloning, Organism; D004305:Dose-Response Relationship, Drug; D046149:Embryo Culture Techniques; D004624:Embryo Transfer / Q000379:methods; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects* / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D006898:Hydroxylamines / Q000494:pharmacology; D053652:Nuclear Transfer Techniques / Q000662:veterinary*; D011804:Quinolines / Q000494:pharmacology; D034421:Sus scrofa / Q000378:metabolism*; D013997:Time Factors
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D006898:Hydroxylamines; D011804:Quinolines; C410733:scriptaid; C012589:trichostatin A; D006655:Histone Deacetylases