title: Trichostatin A rescues the disrupted imprinting induced by somatic cell nuclear transfer in pigs.
abstract: Imprinting disorders induced by somatic cell nuclear transfer (SCNT) usually lead to the abnormalities of cloned animals and low cloning efficiency. Histone deacetylase inhibitors have been shown to improve gene expression, genomic methylation reprogramming and the development of cloned embryos, however, the imprinting statuses in these treated embryos and during their subsequent development remain poorly studied. In this study, we investigated the dynamics of H19/Igf2 methylation and transcription in porcine cloned embryos treated with trichostatin A (TSA), and examined H19/Igf2 imprinting patterns in cloned fetuses and piglets. Our results showed that compared with the maintenance of H19/Igf2 methylation in fertilized embryos, cloned embryos displayed aberrant H19/Igf2 methylation and lower H19/Igf2 transcripts. When TSA enhanced the development of cloned embryos, the disrupted H19/Igf2 imprinting was largely rescued in these treated embryos, more similar to those detected in fertilized counterparts. Further studies displayed that TSA effectively rescued the disrupted imprinting of H19/Igf2 in cloned fetuses and piglets, prevented the occurrence of cloned fetus and piglet abnormalities, and enhanced the full-term development of cloned embryos. In conclusion, our results demonstrated that aberrant imprinting induced by SCNT led to the abnormalities of cloned fetuses and piglets and low cloning efficiency, and TSA rescued the disrupted imprinting in cloned embryos, fetuses and piglets, and prevented the occurrence of cloned fetus and piglet abnormalities, thereby improving the development of cloned embryos. This study would have important implications in improving cloning efficiency and the health of cloned animals.
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin, Heilongjiang Province, China; Dairy Cattle Research Center, Shandong Academy of Agricultural Sciences, Jinan, Shandong Province, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Huan
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin, Heilongjiang Province, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin, Heilongjiang Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin, Heilongjiang Province, China.
authors.forename: Yanshuang
authors.initials: Y
authors.lastname: Mu
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin, Heilongjiang Province, China.
authors.forename: Qingran
authors.initials: Q
authors.lastname: Kong
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin, Heilongjiang Province, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005307:Fertilization in Vitro; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D018392:Genomic Imprinting / Q000187:drug effects* / Q000235:genetics; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D053652:Nuclear Transfer Techniques; D011247:Pregnancy; D013552:Swine
chemical_list: D006877:Hydroxamic Acids; C012589:trichostatin A; D007335:Insulin-Like Growth Factor II