title: Developmental aberrations of liver gene expression in bovine fetuses derived from somatic cell nuclear transplantation.
abstract: Cloning by somatic cell nuclear transfer (NT) has been accomplished. However, the process itself is inefficient since most clones die before birth and survivors often display various anomalies. In an effort to determine global expression profiles of developmentally regulated liver genes in NT bovine fetuses, we employed a custom-made bovine liver complementary DNA (cDNA) microarray. The NT fetuses in early pregnancy were derived from cumulus cells as the nuclear donor cells. Normal fetuses were derived from in vitro fertilization (IVF) and artificial insemination (AI). Gene expression levels in NT, IVF, and AI fetal livers were obtained by comparing individual fetal liver samples with that of adult liver of nonpregnant cycling cows. Statistical analyses of the expression data showed widespread dysregulation of developmentally important genes in the three NT fetuses examined. It was found that the number of dysregulated genes was within a range of 3.5-7.7% of the tested genes in the NT fetal livers. The analyses revealed that one NT fetus was markedly different in liver gene expression profile from the other two NT fetal livers in which the expression profiles were highly correlated. Thus, our findings demonstrate that widespread dysregulation of liver genes occurs in the developing liver of NT bovine fetuses. It is possible that inappropriate genomic reprogramming after NT is a key factor associated with abnormal gene expressions in the livers of NT fetuses, whereas distinct expression patterns between the fellow cloned fetuses likely have resulted from variable epigenetic status of the donor nuclei.
authors.affiliation: Department of Developmental Biology, National Institute of Agrobiological Sciences, Tsukuba City, Ibaraki 305-8602, Japan.
authors.forename: Chandana B
authors.initials: CB
authors.lastname: Herath
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ishiwata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shiojima
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Susumu
authors.initials: S
authors.lastname: Katsuma
authors.forename: Koichi
authors.initials: K
authors.lastname: Ushizawa
authors.forename: Kei
authors.initials: K
authors.lastname: Imai
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Seiya
authors.initials: S
authors.lastname: Takahashi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Izaike
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hashizume
mesh_terms: D000818:Animals; D002417:Cattle / Q000196:embryology* / Q000235:genetics*; D019976:Cloning, Organism; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D020869:Gene Expression Profiling; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy
chemical_list: D018076:DNA, Complementary