title: Valproic acid improved in vitro development of pig cloning embryos but did not improve survival of cloned pigs to adulthood.
abstract: The objective was to examine the effects of valproic acid (VPA), a histone deacetylase inhibitor, on in vitro and in vivo development of Wuzhishan miniature pig somatic cell nuclear transfer (SCNT) embryos. Experiment 1 compared in vitro developmental competence of nuclear transfer embryos treated with various concentrations of VPA for 24 h. Embryos treated with 2 mM VPA for 24 h had a greater rate of blastocyst formation compared with control or embryos treated with 4 or 8 mM VPA (21.5% vs. 10.5%, 12.6%, and 17.2%, P < 0.05). Experiment 2 examined the in vitro developmental competence of nuclear transfer embryos treated with 2 mM VPA for various intervals after chemical activation. Embryos treated for 24 h had higher rates of blastocyst formation than the control or those treated for 4 or 48 h (20.7% vs. 9.2%, 12.1%, and 9.1%, P < 0.05). In Experiment 3, an average of 207 (range, 192-216) nuclear transfer embryos from the VPA-treated group were transferred to surrogate mothers, resulting in three pregnancies. Two of the surrogates delivered a total of 11 live piglets. However, for unknown reasons, nine of 11 piglets in the VPA-treated group died within 1 to 5 d after birth. Untreated control embryos (average, 205; range, 179-225) transferred to four surrogate mothers resulted in three pregnancies, two of which delivered a total of 12 live offspring, although four of 12 piglets in the VPA-untreated group died (cause unknown) within 1 to 3 d, whereas eight of the 12 piglets in the VPA-untreated group survived more than 3 or 4 mo. The average birth weight of the two litters from the VPA-treated group tended (P < 0.05) to be lower than that from the control groups (551.6 g vs. 675.2 g). In conclusion, VPA treatment increased the blastocyst formation rate of SCNT porcine embryos; both VPA-treated and the untreated clones developed to term, but offspring from VPA-treated embryos had a lower survival to adulthood than those from control embryos (18.2% vs. 67.0%; P < 0.05).
authors.affiliation: Department of Animal Science, College of Agriculture, Yanbian University, Yanji, China.
authors.forename: Jin-Dan
authors.initials: JD
authors.lastname: Kang
authors.forename: Suo
authors.initials: S
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.forename: Jun-Xue
authors.initials: JX
authors.lastname: Jin
authors.forename: Yu
authors.initials: Y
authors.lastname: Hong
authors.forename: Chang-Guo
authors.initials: CG
authors.lastname: Yan
authors.forename: Xi-Jun
authors.initials: XJ
authors.lastname: Yin
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000502:physiology; D019976:Cloning, Organism / Q000379:methods*; D046149:Embryo Culture Techniques / Q000662:veterinary; D004624:Embryo Transfer / Q000662:veterinary; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D053652:Nuclear Transfer Techniques / Q000662:veterinary; D011247:Pregnancy; D011256:Pregnancy Outcome; D013552:Swine; D013556:Swine, Miniature / Q000196:embryology* / Q000254:growth & development*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid