title: Aberrant gene expression patterns in placentomes are associated with phenotypically normal and abnormal cattle cloned by somatic cell nuclear transfer.
abstract: Transcription profiling of placentomes derived from somatic cell nuclear transfer (SCNT, n = 20), in vitro fertilization (IVF, n = 9), and artificial insemination (AI, n = 9) at or near term development was performed to better understand why SCNT and IVF often result in placental defects, hydrops, and large offspring syndrome (LOS). Multivariate analysis of variance was used to distinguish the effects of SCNT, IVF, and AI on gene expression, taking into account the effects of parturition (term or preterm), sex of fetus, breed of dam, breed of fetus, and pathological finding in the offspring (hydrops, normal, or other abnormalities). Differential expression of 20 physiologically important genes was confirmed with quantitative PCR. The largest effect on placentome gene expression was attributable to whether placentas were collected at term or preterm (i.e., whether the collection was because of disease or to obtain stage-matched controls) followed by placentome source (AI, IVF, or SCNT). Gene expression in SCNT placentomes was dramatically different from AI (n = 336 genes; 276 >2-fold) and from IVF (n = 733 genes; 162 >2-fold) placentomes. Functional analysis of differentially expressed genes (DEG) showed that IVF has significant effects on genes associated with cellular metabolism. In contrast, DEG associated with SCNT are involved in multiple pathways, including cell cycle, cell death, and gene expression. Many DEG were shared between the gene lists for IVF and SCNT comparisons, suggesting that common pathways are affected by the embryo culture methods used for IVF and SCNT. However, the many unique gene functions and pathways affected by SCNT suggest that cloned fetuses may be starved and accumulating toxic wastes due to placental insufficiency caused by reprogramming errors. Many of these genes are candidates for hydrops and LOS.
authors: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors: Robin E
authors: RE
authors: Everts
authors: Pascale
authors: P
authors: Chavatte-Palmer
authors: Anthony
authors: A
authors: Razzak
authors: Isabelle
authors: I
authors: Hue
authors: Cheryl A
authors: CA
authors: Green
authors: Rosane
authors: R
authors: Oliveira
authors: Xavier
authors: X
authors: Vignon
authors: Sandra L
authors: SL
authors: Rodriguez-Zas
authors: X Cindy
authors: XC
authors: Tian
authors: Xiangzhong
authors: X
authors: Yang
authors: Jean-Paul
authors: JP
authors: Renard
authors: Harris A
authors: HA
authors: Lewin
mesh_terms: D000818:Animals; D002417:Cattle / Q000235:genetics*; D002478:Cells, Cultured; D019976:Cloning, Organism; D016000:Cluster Analysis; D004622:Embryo, Mammalian; D005260:Female; D005307:Fertilization in Vitro; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053652:Nuclear Transfer Techniques; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy