Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DNA methylation profiling of placental villi from karyotypically normal recurrent miscarriage

ABSTRACT: Miscarriage occurs in 15-20% of clinical pregnancies. While chromosomal errors are observed in over 50%, causes of karyotypically normal losses are poorly understood. DNA methylation undergoes reprogramming during development and must be appropriately set to maintain a healthy pregnancy. We hypothesize that aberrant DNA methylation may cause karyotypically normal miscarriage, particularly among women experiencing recurrent miscarriage (RM). DNA methylation in first trimester chorionic villi was assessed in chromosomally normal miscarriages from women with RM (N=33) or isolated miscarriage (M, N=21), and elective terminations (TA, N=16). Differentially methylated candidate loci were identified using the Illumina Infinium HumanMethylation27 BeadChip array by comparing 10 RM to 10 TA samples. Follow up showed a significant increase in methylation in RM and M compared to TA placentae at the CYP1A2 (p=0.002) and AXL (p=0.02) promoters and decrease at the DEFB1 (p=0.008) promoter. Gene function analysis showed an enrichment of imprinted genes (p=9.53E-10) and genes previously associated with RM (p=9.51E-06). DNA methylation was evaluated at 7 imprinted loci using bisulfite pyrosequencing. An increase of outliers at these loci was observed in RM (3.9%) compared to M (0%) and TA (0.9%) (p=0.02), with increased average methylation at the H19/IGF2 ICR1 in M samples (p<0.0001). Altered DNA methylation in the placenta at specific loci, as well as global dysregulation in specific cases, may contribute to or be a consequence of placental insufficiency in karyotypically normal miscarriage.

ORGANISM(S): Homo sapiens

PROVIDER: GSE43256 | GEO | 2016/01/02

SECONDARY ACCESSION(S): PRJNA185153

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

DNA methylation profiling of placental villi from karyotypically normal recurrent miscarriage

Project description:Miscarriage occurs in 15-20% of clinical pregnancies. While chromosomal errors are observed in over 50%, causes of karyotypically normal losses are poorly understood. DNA methylation undergoes reprogramming during development and must be appropriately set to maintain a healthy pregnancy. We hypothesize that aberrant DNA methylation may cause karyotypically normal miscarriage, particularly among women experiencing recurrent miscarriage (RM). DNA methylation in first trimester chorionic villi was assessed in chromosomally normal miscarriages from women with RM (N=33) or isolated miscarriage (M, N=21), and elective terminations (TA, N=16). Differentially methylated candidate loci were identified using the Illumina Infinium HumanMethylation27 BeadChip array by comparing 10 RM to 10 TA samples. Follow up showed a significant increase in methylation in RM and M compared to TA placentae at the CYP1A2 (p=0.002) and AXL (p=0.02) promoters and decrease at the DEFB1 (p=0.008) promoter. Gene function analysis showed an enrichment of imprinted genes (p=9.53E-10) and genes previously associated with RM (p=9.51E-06). DNA methylation was evaluated at 7 imprinted loci using bisulfite pyrosequencing. An increase of outliers at these loci was observed in RM (3.9%) compared to M (0%) and TA (0.9%) (p=0.02), with increased average methylation at the H19/IGF2 ICR1 in M samples (p<0.0001). Altered DNA methylation in the placenta at specific loci, as well as global dysregulation in specific cases, may contribute to or be a consequence of placental insufficiency in karyotypically normal miscarriage. First-trimester placental villi samples from karyotypically normal miscarriages from recurrent miscarriage patients (N, N=10) and chromosomally normal elective terminations (PZET, N=10).

2016-07-04 | E-GEOD-43256 | biostudies-arrayexpress

Increased placental expression and maternal serum levels of apoptosis-inducing TRAIL in recurrent miscarriage

Project description:INTRODUCTION: Recurrent miscarriage (RM; ≥3 consecutive pregnancy losses) occurs in 1-3% of fertile couples. No biomarkers with high predictive value of threatening miscarriage have been identified. We aimed to profile whole-genome differential gene expression in RM placental tissue, and to determine the protein levels of identified loci in maternal sera in early pregnancy. METHODS: GeneChips (Affymetrix(®)) were used for discovery and Taqman RT-qPCR assays for replication of mRNA expression in placentas from RM cases (n = 13) compared to uncomplicated pregnancies matched for gestational age (n = 23). Concentrations of soluble TRAIL (sTRAIL) and calprotectin in maternal serum in normal first trimester (n = 35) and failed pregnancies (early miscarriage, n = 18, late miscarriage, n = 4; tubal pregnancy, n = 11) were determined using ELISA. RESULTS: In RM placentas 30 differentially expressed (with nominal P-value < 0.05) transcripts were identified. Significantly increased placental mRNA expression of TNF-related apoptosis-inducing ligand (TRAIL; P = 1.4 × 10(-3); fold-change 1.68) and S100A8 (P = 7.9 × 10(-4); fold-change 2.56) encoding for inflammatory marker calprotectin (S100A8/A9) was confirmed by RT-qPCR. When compared to normal first trimester pregnancy (sTRAIL 16.1 ± 1.6 pg/ml), significantly higher maternal serum concentration of sTRAIL was detected at the RM event (33.6 ± 4.3 pg/ml, P = 0.00027), and in pregnant women, who developed an unpredicted miscarriage 2-50 days after prospective serum sampling (28.5 ± 4.4 pg/ml, P = 0.039). Women with tubal pregnancy also exhibited elevated sTRAIL (30.5 ± 3.9 pg/ml, P = 0.035). Maternal serum levels of calprotectin were neither diagnostic nor prognostic to early pregnancy failures (P > 0.05). CONCLUSIONS: The study indicated of sTRAIL as a potential predictive biomarker in maternal serum for early pregnancy complications.

2010-12-31 | GSE22490 | GEO

Genome-wide parent-of-origin DNA methylation analysis [Methyl-seq]

Project description:Genomic imprinting is a form of epigenetic regulation that results in expression of either the maternally or paternally inherited allele of a subset of genes. Imprinted loci contain differentially methylated regions (DMRs) where cytosine methylation marks one of the parental alleles, providing cis-acting regulatory elements that influence the allelic expression of surrounding genes, however to date the total number of imprinted loci within the human genome is unknown. To characterize known imprinted DMRS and identify novel imprinted loci we have performed whole-genome bisulphite sequencing and high-resolution DNA methylation array analysis of healthy tissues. Sequencing of bisulfite converted DNA analysis of normal brain (white matter), liver and term placenta tissue

2013-12-28 | E-GEOD-46698 | biostudies-arrayexpress

Genome-wide parent-of-origin DNA methylation analysis [Methylation450 BeadChip]

Project description:Genomic imprinting is a form of epigenetic regulation that results in expression of either the maternally or paternally inherited allele of a subset of genes. Imprinted loci contain differentially methylated regions (DMRs) where cytosine methylation marks one of the parental alleles, providing cis-acting regulatory elements that influence the allelic expression of surrounding genes, however to date the total number of imprinted loci within the human genome is unknown. To characterize known imprinted DMRS and identify novel imprinted loci we have performed whole-genome bisulphite sequencing and high-resolution DNA methylation array analysis of healthy tissues. Sequencing of bisulfite converted DNA and array based analysis of normal tissues, human embryonic stem cells, androgenetic hydatidiform moles and leukocytes from reciprocal genome-wide uniparental disomies.

2013-12-28 | E-GEOD-52576 | biostudies-arrayexpress

DNA methylation changes in Dnmt3L-deficient mouse embryonic stem cells (mESCs)

Project description:We used RRBS to analyze DNA methylation in mESC lines deficient for maternal Dnmt3L (Dnmt3L mKO), zygotic Dnmt3L (Dnmt3L KO), and both maternal and zygotic Dnmt3L (Dnmt3L mzKO). Compared to wild-type (WT) mESCs, Dnmt3L mKO mESCs exhibit severe loss of methylation at imprinted loci but no changes in global DNA methylation, Dnmt3L KO mESCs exhibit moderate loss of methylation at many Dnmt3a target regions but do not affect methylation at imprinted loci, and Dnmt3L mzKO mESCs exhibit combined changes of mKO and KO cells, with severe loss of methylation at imprinted loci and moderate loss of methylation at Dnmt3a target regions.

2018-10-04 | GSE116489 | GEO

Methylation profiling defines a widespread field defect in histologically normal prostate tissue associated with prostate cancer

Project description:We evaluated the presence of genome-wide epigenetic differences at 385,000 loci using Encode HG18 DNA methylation arrays in 5 non-tumor-associated (NTA) and 4 histologically undistinguished tumor-associated (TA) prostate tissues. We identified 615 probes to be differentially methylated (p<0.05) in TA prostate, with 537 (87%) hypomethylated and 78 (13%) hypermethylated. comparison of methylation in NTA to TA prostate tissue

2012-06-27 | E-GEOD-38982 | biostudies-arrayexpress

Genome-wide parent-of-origin DNA methylation analysis [Methylation450 BeadChip]

2013-12-28 | GSE52576 | GEO

Genome-wide parent-of-origin DNA methylation analysis [Methyl-seq]

2013-12-28 | GSE46698 | GEO

DNA methylation profiling in recurrent miscarriage

Project description:DNA methylation profiling in recurrent miscarriage

| PRJNA593016 | ENA

Methylation profiling defines a widespread field defect in histologically normal prostate tissue associated with prostate cancer

2012-06-28 | GSE38982 | GEO