Effects of Assisted Reproduction Technology on Placental Imprinted Gene Expression

We used placental tissue to compare the imprinted gene expression of IGF2, H19, KCNQ1OT1, and CDKN1C of singletons conceived via assisted reproduction technology (ART) with that of spontaneously conceived (SC) singletons. Of 989 singletons examined (ART ; SC ), neonatal weight was significantly lower in the ART group than in the SC group, but placental weight showed no significant difference. Gene expression analyzed by real-time PCR was similar for both groups with appropriate-for-date (AFD) birth weight. H19 expression was suppressed in fetal growth retardation (FGR) cases in the ART and SC groups compared with AFD cases ( and , resp.). In contrast, CDKN1C expression was suppressed in FGR cases in the ART group , while KCNQ1OT1 expression was hyperexpressed in FGR cases in the SC group . As imprinted gene expression patterns differed between the ART and SC groups, we speculate that ART modifies epigenetic status even though the possibilities always exist.

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Imprinted gene expression analysis in cases with low birth weight after assisted reproduction technology

Fertility and Sterility ◽

10.1016/j.fertnstert.2008.07.847 ◽

2008 ◽

Vol 90 ◽

pp. S71 ◽

Cited By ~ 1

Author(s):

Y. Katagiri ◽

C. Aoki ◽

Y. Fukuda ◽

N. Takeshita ◽

M. Tanaka ◽

...

Keyword(s):

Gene Expression ◽

Birth Weight ◽

Low Birth Weight ◽

Assisted Reproduction ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Imprinted Gene ◽

Assisted Reproduction Technology

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Expression of placental regulatory genes is associated with fetal growth

Journal of Perinatal Medicine ◽

10.1515/jpm-2017-0064 ◽

2017 ◽

Vol 45 (7) ◽

Cited By ~ 9

Author(s):

Maya A. Deyssenroth ◽

Qian Li ◽

Marina Lacasaña ◽

Yoko Nomura ◽

Carmen Marsit ◽

...

Keyword(s):

Gene Expression ◽

Birth Weight ◽

Fetal Growth ◽

Gestational Age ◽

Expression Patterns ◽

Regulatory Genes ◽

Differentially Expressed ◽

Gene Expression Patterns ◽

Metabolic Functions

AbstractThe placenta is the principal organ regulating respiratory, nutritional, endocrine and metabolic functions on behalf of the developing fetus. Changes in gene expression patterns of placenta-specific genes may influence fetal growth. We profiled the expression of 17 genes related to placenta functioning in term placentas (n=677) to identify genes differentially expressed across birth weight categories [small (SGA), appropriate (AGA) and large (LGA) for gestational age].

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26ABERRANT REPROGRAMMING OF IMPRINTED GENE EXPRESSION IN ENLARGED PLACENTAS OF MICE CLONED FROM ES CELLS TREATED WITH TSA OR 5AZAC

Reproduction Fertility and Development ◽

10.1071/rdv16n1ab26 ◽

2004 ◽

Vol 16 (2) ◽

pp. 135

Author(s):

S.G. Baqir ◽

Q. Zhou ◽

A. Jouneau ◽

J.-P. Renard ◽

D.H. Betts ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Histone Acetylation ◽

Nuclear Transfer ◽

Es Cells ◽

Expression Patterns ◽

Gene Expression Patterns ◽

Imprinted Genes ◽

Imprinted Gene ◽

Donor Cells

The success rate of producing cloned animals is very low, and in many cases is associated with the formation of enlarged placentas. Increasing evidence has pointed towards epigenetic deregulation of imprinted genes due to incomplete or abnormal resetting of DNA methylation and/or histone acetylation patterns during development. It has previously been shown that drugs that alter DNA methylation (5AzaC) and histone acetylation (TSA) over-express imprinted genes in mouse ES cells (Baqir and Smith, 2001, Theriogenology 55, 410). Our objective in this study was to determine whether nuclear transfer is able to reprogram imprinted gene expression patterns in the placenta of mice cloned from ES donor nuclei exposed to 5AzaC and TSA. ES donor cells were treated with either TSA or 5AzaC prior to injection into enucleated oocytes. Total RNA was extracted from placentas of day 14–15 fetus clones, and reversed transcribed; the expression pattern of imprinted genes (Ipl, Mash2, Igf2, H19, Igf2r, p57, Peg1), non-imprinted placental-specific genes (Esx1, Dlx3, Tpbp) and a housekeeping gene (Gapdh) was examined by Real Time PCR. Samples were standardized with an exogenous control (Globin) and expressed as fold changes in relation to placentas of cloned fetus derived from non-treated donor cells. Data were analyzed by ANOVA and mean gene expression values were compared using the Tukey-Kramer test. Our results show that several imprinted genes (Mash2, H19, Ipl) and placenta-specific genes (Esx1 and Dlx1) were properly reprogrammed in non-enlarged (71mg) placentas of fetus clones derived from the TSA and 5AzaC treated ES donor cells. Although Gapdh expression did not differ among normal and enlarged 210mg) placenta groups, the expression level of Igf2 and Mash2 was higher in enlarged placentas from fetus clones produced from TSA-treated ES donor cells (4.6 and 3.5 fold) compared to non-enlarged placentas from non-treated ES cells (1 fold). Conversely, oversized placentas from cloned fetuses derived from TSA-treated donor ES cells under-expressed Peg1, H19 and Ipl (0.5, 0.2 and 0.2 fold, respectively) compared to control placentas (1 fold). In addition, enlarged placentas from the TSA- and 5AzaC-treated group displayed down-regulation of placenta specific genes Esx1 and Dlx3 and up-regulation of Tpbp, suggesting the presence of abnormal distribution of placental layers. These results indicate that while several imprinted and non-imprinted placenta specific genes were correctly expressed in normal size placentas of fetus clones derived from TSA and 5AzaC treated donor ES cells, enlarged placentas displayed aberrant gene expression patterns, suggesting that improper resetting of the epigenetic program after nuclear transfer is directly related to altered DNA methylation and histone acetylation patterns. Funded by NSERC & CIHR.

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Investigation of Fasciculation and Elongation Protein ζ-1 (FEZ1) in Peripheral Blood Reveals Differences in Gene Expression in Patients with Schizophrenia

Balkan Journal of Medical Genetics ◽

10.1515/bjmg-2015-0003 ◽

2015 ◽

Vol 18 (1) ◽

pp. 31-38 ◽

Cited By ~ 1

Author(s):

T.I. Vachev ◽

V.K. Stoyanova ◽

H.Y. Ivanov ◽

I.N. Minkov ◽

N.T. Popov

Keyword(s):

Gene Expression ◽

Peripheral Blood ◽

Current Knowledge ◽

Expression Patterns ◽

Pcr Analysis ◽

Gene Expression Patterns ◽

Down Regulation ◽

Blood Samples ◽

Molecular Abnormalities ◽

Significant Difference

Abstract Schizophrenia (SZ) is a chronic neuropsychiatric disorder characterized by affective, neuromorphological and cognitive impairment, deteriorated social functioning and psychosis with underlying molecular abnormalities, including gene expression changes. Observations have suggested that fasciculation and elongation protein ζ-1 (FEZ1) may be implicated in the pathogenesis of schizophrenia. Nevertheless, our current knowledge of the expression of FEZ1 in peripheral blood of schizophrenia patients remains unclear. The purpose of this study was to identify the characteristic gene expression patterns of FEZ1 in peripheral blood samples from schizophrenia patients. We performed quantitative reverse-transcriptase (qRT-PCR) analysis using peripheral blood from drug-free schizophrenia patients (n = 29) and age and gender-matched general population controls (n = 24). For the identification of FEZ1 gene expression patterns, we applied a comparative threshold cycle (CT) method. A statistically significant difference of FEZ1 mRNA level was revealed in schizophrenia subjects compared to healthy controls (p = 0.0034). To the best of our knowledge, this study is the first describing a down-regulation of FEZ1 gene expression in peripheral blood of patients with schizophrenia. Our results suggested a possible functional role of FEZ1 in the pathogenesis of schizophrenia and confirmed the utility of peripheral blood samples for molecular profiling of psychiatric disorders including schizophrenia. The current study describes FEZ1 gene expression changes in peripheral blood of patients with schizophrenia with significantly down-regulation of FEZ1 mRNA. Thus, our results provide support for a model of SZ pathogenesis that includes the effects of FEZ1 expression.

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40 PIG CLONING AND GENE EXPRESSION PATTERNS IN MINIPIG ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS

Reproduction Fertility and Development ◽

10.1071/rdv25n1ab40 ◽

2013 ◽

Vol 25 (1) ◽

pp. 168

Author(s):

M. J. Kim ◽

H. J. Oh ◽

J. E. Park ◽

G. A. Kim ◽

E. J. Park ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Expression Patterns ◽

Donor Cell ◽

Total Cell ◽

Laboratory Animals ◽

Gene Expression Patterns ◽

Significant Difference

In several laboratory animals and humans, adipose tissue-derived mesenchymal stem cells (ASC) are very interesting; they are easy to harvest and can expand to generate millions of cells from a small quantity of fat. The ASC are known as useful materials for clinical applications in human cell therapy and as a donor cell in somatic cell nuclear transfer (SCNT). In this study, we investigated the expression patterns of several genes (Oct-4, Nanog, Sox2, Dnmt1, and Dnmt3b) in minipig ASC, and whether ASC can be a suitable donor cell type for producing cloned pigs. For the study, we respectively isolated ASC, adult skin fibroblast (ASF) and fetal fibroblast (FF) from a 6-year-old female minipig. The ASC were attached to a plastic dish with a fibroblast-like morphology, expressed cell-surface marker characteristics of stem cells, and underwent osteogenic, adipogenic, and neurogenic differentiation when exposed to specific differentiation-inducing conditions. To observe gene expression, total RNA was extracted from ASC, FF, and ASF, respectively, and was used for reverse transcription (RT). After RT, real-time PCR was performed to investigate the expression of Oct-4, Sox2, Nanog, Dnmt1, and Dnmt3b. The expression of β-actin was measured and used as an endogenous control. In the following experiment, we carried out SCNT using ASC, ASF, and FF. The ratio of blastocysts to 2-cell embryos and total cell number of blastocysts were monitored as experimental parameters. Statistical analysis was performed using one-way ANOVA (GraphPad Prism version 5). As a result, the relative abundance of DNMT1 in ASC (1.9 ± 0.9) was significantly higher than that in FF and ASF (0.1 ± 0.2 and 1.0 ± 0.5, respectively; P < 0.05), but no significant difference in expression of the DNMT3b gene was observed. Interestingly, the quantity of Oct-4 was significantly higher in FF and ASC than in ASF (2.8 ± 0.4 and 2.9 ± 0.5 v. 1.0 ± 0.1, respectively; P < 0.05), and Sox2 showed significantly higher expression in ASC (3.7 ± 0.5) than in ASF and FF (1.0 ± 0.1 and 1.4 ± 0.6, respectively; P < 0.05). Nanog expression was similar in ASF, FF, and ASC. After SCNT, the developmental competence to blastocysts did not differ among the 3 groups (ASF: 7.0 ± 0.2%, FF: 16.15 ± 6.1%, and ASC: 11.1 ± 0.7%). However, total cell numbers of blastocysts derived from ASC and FF were significantly higher in ASF (89.0 ± 7.9 and 105.0 ± 5.5 v. 57.5 ± 5.2, respectively). In conclusion, the present study revealed that minipig ASC and minipig FF possess slightly different gene expression patterns and ASC have potential in terms of in vitro development and blastocyst formation ability similar to ASF and FF. This study was supported by IPET (no. 311011-05-1-SB010), RDA (no. PJ0089752012), RNL Bio (no. 550-20120006), Institute for Veterinary Science, and the BK21 program.

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