Abnormal Expression of TIMP‐2, SOD, Vimentin and PAI Proteins in Cloned Bovine Placentae

Kim, H. R.; Naruse, Kenji; Lee, H. R.; Han, Rong Xun; Park, C. S.; Jin, D. I.

doi:10.1111/j.1439-0531.2007.01058.x

Cited by 8 publications

(13 citation statements)

References 24 publications

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“…This suggests that H3-K9/ K14 histone acetylation may be important for regulation of TIMP-2 and PBEF gene expression in the developing mouse placenta. Thus, our present results support the notion that cloned placentae probably appear to suffer from failed reprogramming of histone modifications in developmentally important genes, leading to aberrant expression of their protein products and changes in TIMP-2 and PBEF expression are likely to be involved in the placental abnormalities seen among cloned mice and cows (e.g., enlargement and/or improper functionality) (8)(9)(10).…”

Section: Discussionsupporting

confidence: 77%

“…Consistent with this hypothesis, recent studies have shown that errors in the epigenetic reprogramming of the somatic cell genome can result in the dysregulated expression of developmentally imprinted genes in cloned embryos, fetuses and placentae, leading to abnormalities in the resulting cloned animals (4)(5)(6). In this context, numerous groups have reported abnormal gene expression patterns related to somatic cell nuclear transfer (7)(8)(9)(10). However, the existence, importance and regulation of abnormal gene expression through epigenetic modification have not yet been fully elucidated in the context of placentation.…”

Section: Introductionmentioning

confidence: 57%

“…We previously reported the aberrant expression of TIMP-2 and PBEF in cloned bovine and mouse placentae, particularly at the end of gestation (8)(9)(10). TIMP-2 was related to trophoblastic invasion and extracellular matrix (ECM) remolding during pregnancy (14).…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic characterization of the PBEF and TIMP-2 genes in the developing placentae of normal mice

Kim

Han²,

Diao³

et al. 2011

BMB Reports

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Reprogramming errors, which appear frequently in cloned animals, are reflected by aberrant gene expression. We previously reported the aberrant expression of TIMP-2 and PBEF in cloned placenta and differential expression of PBEF genes during pregnancy. To examine the epigenetic modifications that regulate dynamic gene expression in developing placentae, we herein analyzed the mRNA and protein expression levels of PBEF and TIMP-2 in the placentae of normal mice during pregnancy and then examined potential correlations with epigenetic modifications. DNA methylation pattern analysis revealed no difference, but ChIP assays using antibodies against H3-K9/K14 and H4-K5 histone acetylation revealed that the H3-K9/K14 acetylation levels, but not the H4-K5 acetylation levels, of the TIMP-2 and PBEF loci were significantly correlated with their gene expression levels during placentation in normal mice. These results suggest that epigenetic changes may regulate gene expression level in the developing placentae of normal mice and that inappropriate epigenetic reprogramming might be one cause of the abnormal placentae seen in cloned animals. [BMB reports 2011; 44(8): 535-540]

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 57%

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Epigenetic characterization of the PBEF and TIMP-2 genes in the developing placentae of normal mice

Kim

Han²,

Diao³

et al. 2011

BMB Reports

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“…This study also confirmed other studies showing that placentomes from apparently non-pathological clones were over the normal weight range (see EFSA 2009, EFSA 2008. Aberrant gene expression has been reported in the bovine placenta, in a study that analysed placenta from three clones that died immediately after birth (Kim et al, 2009a). In this study placentas from artificial insemination were used as controls instead of placentas from live born clones.…”

Section: Aberrant Gene Expression In Placentamentioning

confidence: 99%

Update on the state of play of animal cloning

2010

EFSA Journal

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The European Food Safety Authority (EFSA) received in May 2010, a request from the European Commission for an update on the state of play of the possible scientific developments on the issue of cloning of farmed animals for food production purposes. The present statement follows the EFSA 2009 statement and EFSA 2008 scientific opinion and is based on a review of identified peer reviewed scientific literature up to 1 July 2010, information made available to EFSA following a call for data, discussion with experts in the field of animal cloning and a peer review by external experts. Based on the literature search and information provided, it is concluded that there is still limited information available on species other than cattle and pigs which would allow for assessment of food safety and animal health and welfare aspects. Cloning efficiency in cattle (currently around 10 %) and pigs (currently around 6 %) is lower than by natural breeding (cattle calving rate 40-55 %) as well as from assisted reproductive technologies (ART), such as artificial insemination. However, compared with in vitro produced embryos and embryo transfer in pigs, cloning has similar efficiency (~ 6 %). No new information has become available, since the EFSA 2009 statement and the EFSA 2008 scientific opinion that would lead, at this point in time, to a reconsideration of the conclusions and recommendations related to the food safety, animal health and welfare aspects of animal cloning as considered in the 2008 scientific opinion and the EFSA 2009 statement.

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“…Consistent with this hypothesis, errors in the epigenetic reprogramming of the somatic cell genome have been associated with the expressional dysregulation of developmentally imprinted genes in cloned embryos, fetuses and placentae, and abnormalities in the resulting cloned animals [11,12,13,14,15]. In this context, numerous researchers have observed abnormal gene expression patterns following somatic cell nuclear transfer [16,17,18,19]. However, the existence, importance, and regulation of epigenetic modification-related abnormalities in gene expression have not yet been fully elucidated in the context of placentation.…”

Section: Introductionmentioning

confidence: 99%

Aberrant Expression of TIMP-2 and PBEF Genes in the Placentae of Cloned Mice Due to Epigenetic Reprogramming Error

et al. 2016

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Cloned mice derived from somatic or ES cells show placental overgrowth (placentomegaly) at term. We had previously analyzed cloned and normal mouse placentae by using two-dimensional gel electrophoresis and mass spectrometry to identify differential protein expression patterns. Cloned placentae showed upregulation of tissue inhibitor of metalloproteinase-2 (TIMP-2), which is involved in extracellular matrix degradation and tissue remodeling, and downregulation of pre-B cell colony enhancing factor 1 (PBEF), which inhibits apoptosis and induces spontaneous labor. Here, we used Western blotting to further analyze the protein expression levels of TIMP-2 and PBEF in cloned placentae derived from cumulus cells, TSA-treated cumulus cells, intracytoplasmic sperm injection (ICSI), and natural mating (NM control). Cloned and TSA-treated cloned placentae had higher expression levels of TIMP-2 compared with NM control and ICSI-derived placentae, and there was a positive association between TIMP-2 expression and the placental weight of cloned mouse concepti. Conversely, PBEF protein expression was significantly lower in cloned and ICSI placentae compared to NM controls. To examine whether the observed differences were due to abnormal gene expression caused by faulty epigenetic reprogramming in clones, we investigated DNA methylation and histone modification in the promoter regions of the genes encoding TIMP-2 and PBEF. Sodium bisulfite sequencing did not reveal any difference in DNA methylation between cloned and NM control placentae. However, ChIP assays revealed that the level of H3-K9/K14 acetylation at the TIMP-2 locus was higher in cloned placentae than in NM controls, whereas acetylation of the PBEF promoter was lower in cloned and ICSI placenta versus NM controls. These results suggest that cloned placentae appear to suffer from failure of histone modification-based reprogramming in these (and potentially other) developmentally important genes, leading to aberrant expression of their protein products. These changes are likely to be involved in generating the abnormalities seen in cloned mouse placentae, including enlargement and/or a lack of proper placental function.

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Abnormal Expression of TIMP‐2, SOD, Vimentin and PAI Proteins in Cloned Bovine Placentae

Cited by 8 publications

References 24 publications

Epigenetic characterization of the PBEF and TIMP-2 genes in the developing placentae of normal mice

Epigenetic characterization of the PBEF and TIMP-2 genes in the developing placentae of normal mice

Update on the state of play of animal cloning

Aberrant Expression of TIMP-2 and PBEF Genes in the Placentae of Cloned Mice Due to Epigenetic Reprogramming Error

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