Global gene expression analysis of bovine somatic cell nuclear transfer blastocysts and cotyledons

Aston, Kenneth I.; Li, G.P.; Hicks, Brady A.; Sessions, Benjamin R.; Davis, Aaron P.; Winger, Quinton A.; Rickords, Lee F.; Stevens, John R.; White, Kenneth L.

doi:10.1002/mrd.20962

Cited by 19 publications

(12 citation statements)

References 64 publications

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“…These results suggest that immune responses of the endometrium to the SCNTderived conceptus may be dysregulated, and such dysregulation has been suggested as a major cause of inadequate placentome development that leads to immune-mediated abortion in cloned pregnancies (26). Indeed, MHC1 is overexpressed in SCNT-derived blastocysts and placentas (26,27). Furthermore, differential mRNA expression was found for 2 steroid hydroxylase genes [cytochrome P450, family 27, subfamily A, polypeptide 1 (CYP27A1), cytochrome P450, family 39, subfamily a, polypeptide 1 (CYP39A1)] and a number of transcription factors, such as SRY (sex determining region Y)-box 4 (SOX4) and 17 (SOX17), and RAR-related orphan receptor B (RORB).…”

Section: Discussionmentioning

confidence: 95%

The endometrium responds differently to cloned versus fertilized embryos

Bauersachs

Ulbrich

Zakhartchenko³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

193

144

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Although somatic cell nuclear transfer (SCNT) cloning is more efficient in cattle than in any other species tested so far, there is a high rate of pregnancy failure that has been linked to structural and functional abnormalities of the placenta. We tested the hypothesis that these changes may originate from disturbed embryo-maternal interactions in the peri-implantation period. Therefore, we evaluated the response of the endometrium to SCNT embryos (produced from 7 different fetal fibroblast cell lines) as compared with embryos derived from in vitro fertilization (IVF). SCNT embryos and IVF embryos were cultured under identical conditions to the blastocyst stage (day 7) and were transferred to corresponding recipients, which were slaughtered at day 18 of pregnancy. The mRNA profiles of endometrium samples were obtained using a custom cDNA microarray enriched for transcripts differentially expressed in the endometrium and/or oviduct epithelium during the estrous cycle and/or early pregnancy. Overall, the variation in mRNA profiles was greater in the SCNT group than in the IVF group. Furthermore, 58 transcripts were differentially abundant in endometria from SCNT and IVF pregnancies. Prominent examples are orphan nuclear receptor COUP-TFII and connexin 43, both known to play important roles in uterine receptivity and conceptus placentation. These findings suggest that placental failure in bovine clone pregnancies may originate from abnormal embryomaternal communication that develops during the peri-implantation period. Endometrium transcriptome profiles may serve as a tool to evaluate SCNT embryos for their ability to establish pregnancy and develop a functional placenta.Bos taurus ͉ cloning ͉ early pregnancy ͉ gene expression ͉ microarray C loning by somatic cell nuclear transfer (SCNT) (1) is an important strategic tool for animal breeding and biotechnology. For example, animals carrying rare desired alleles can be multiplied to introduce the desired allele into the breeding population. The life span and capacity of valuable breeding animals and the physiologically limited number of offspring of female animals can be increased, thus enhancing selection intensity. Moreover, cloning allows the propagation of desired genotypes without the risk of genetic recombination that is inherent to sexual reproduction. In animal biotechnology, SCNT using genetically modified donor cells is a powerful approach for the generation of transgenic animals (2) and so far is the only technique facilitating targeted mutagenesis in livestock species (3). Moreover, cloning can be used to multiply transgenic animals and to propagate multitransgenic individuals without segregation of the individual transgenes.Despite the plethora of important applications of cloning, the efficiency of this technology still is very low. Although SCNT is more efficient in cattle than in any other species tested so far, a recent survey covering the results of bovine cloning in Brazil, Argentina, and the United States over a 5-year period revealed that only 9...

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Section: Discussionmentioning

confidence: 95%

The endometrium responds differently to cloned versus fertilized embryos

Bauersachs

Ulbrich

Zakhartchenko³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

193

144

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“…Overall 36% of the 377 miRNAs studied were differentially regulated between IVP and AI placentas, of which about 96% were downregulated in IVP placentas. These massive deregulations could be entailed to the reported radically altered gene expression in cloned placenta [17,18] associated to poor placentome development in NT pregnancies in the first trimester leading to subsequent pregnancy loss.…”

Section: Discussionmentioning

confidence: 99%

Massive deregulation of miRNAs from nuclear reprogramming errors during trophoblast differentiation for placentogenesis in cloned pregnancy

et al. 2014

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BackgroundLow efficiency of Somatic Cell Nuclear Transfer (NT) has been widely addressed with high incidence of placental abnormalities due to genetic and epigenetic modifications. MiRNAs are shown to be major regulators of such modifications. The present study has been carried out to identify the expression patterns of 377 miRNAs, their functional associations and mechanism of regulation in bovine placentas derived from artificial insemination (AI), in vitro production (IVP) and NT pregnancies.ResultsThis study reveals a massive deregulation of miRNAs as chromosomal cluster or miRNA families without sex-linkage in NT and in-vitro derived IVP placentas. Cell specific localization miRNAs in blastocysts and expression profiling of embryos and placentas at different developmental stages identified that the major deregulation of miRNAs exhibited in placentas at day 50 of pregnancies is found to be less dependent on global DNA methylation, rather than on aberrant miRNA biogenesis molecules. Among them, aberrant AGO2 expression due to hypermethylation of its promoter was evident. Along with other factors, aberrant AGO2 expression was observed to be associated with multiple defects in trophoblast differentiation through deregulation of miRNAs mediated mechanisms.ConclusionThese aberrant miRNA activities might be associated with genetic and epigenetic modifications in abnormal placentogenesis due to maldifferentiation of early trophoblast cell lineage in NT and IVP pregnancies. This study provides the first insight into genome wide miRNA expression, their role in regulation of trophoblast differentiation as well as abnormal placental development in Somatic Cell Nuclear Transfer pregnancies to pave the way to improve the efficiency of cloning by nuclear transfer.

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“…Aberrant gene expression patterns in bovine blastocysts, placentomes and cotyledons have been reported (Everts et al, 2008;Aston et al, 2009). Differentially expressed genes (DEG) associated with SCNT are involved in multiple biological pathways including cell cycle, cell death and gene expression.…”

Section: Gene Expression Imprinting and Biomarkersmentioning

confidence: 99%

Further Advice on the Implications of Animal Cloning (SCNT)

2009

EFS2

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Global gene expression analysis of bovine somatic cell nuclear transfer blastocysts and cotyledons

Cited by 19 publications

References 64 publications

The endometrium responds differently to cloned versus fertilized embryos

The endometrium responds differently to cloned versus fertilized embryos

Massive deregulation of miRNAs from nuclear reprogramming errors during trophoblast differentiation for placentogenesis in cloned pregnancy

Further Advice on the Implications of Animal Cloning (SCNT)

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