Project description:Genome wide placental DNA methylation profiling of full term and preterm deliveries sampled from 5 full term deliveries and 4 preterm deliveries. The Illumina HumanMethylation450 Beadchip was used to obtain DNA methylation profiles across approximately 485,577 CpGs in formalin fixed samples. Samples included 4 placental tissues from 4 women with preterm delivery and 5 placental tissues from 5 women with full term delivery. 9 women's placental DNA (4 women had perterm deliveries and 5 women had full term deliveries) were hybridised to the Illumina HumanMethylation450 Beadchip
Project description:Genome wide placental DNA methylation profiling of full term and preterm deliveries sampled from 5 full term deliveries and 4 preterm deliveries. The Illumina HumanMethylation450 Beadchip was used to obtain DNA methylation profiles across approximately 485,577 CpGs in formalin fixed samples. Samples included 4 placental tissues from 4 women with preterm delivery and 5 placental tissues from 5 women with full term delivery.
Project description:Placental insufficiency is implicated in the intrauterine infection-associated spontaneous preterm birth. Using a mouse model of LPS-induced intrauterine inflammation that leads to preterm delivery, RNA-seq study was performed in the placenta at gestational day 17 to assess the transcriptome changes.
Project description:The amniotic fluid (AF) cell-free (cf) RNA was shown to reflect physiological and pathological processes in pregnancy, but its value in prediction of spontaneous preterm delivery is unknown. Here we profiled cfRNA in AF samples collected from women who underwent transabdominal amniocentesis after an episode of spontaneous preterm labor and subsequently delivered within 24h (n=10) or later (n=28) in gestation. Expression of known placental single cell (sc) RNA-Seq signatures were quantified in AF cfRNA and compared between groups. Random forest models were applied to predict time to delivery after amniocentesis. There were 2385 genes differentially expressed in AF samples of women who delivered within 24 hours of amniocentesis compared to gestational age-matched samples from women who delivered after 24 hours of amniocentesis.Genes with cfRNA changes were associated with immune and inflammatory processes related to the onset of labor, and expression of placental scRNA-Seq signatures of immune cells were increased with imminent delivery. AF transcriptomic prediction models captured these effects and predicted delivery within 24 hours of amniocentesis (AUROC =0.81). These results may inform development of biomarkers for spontaneous preterm birth.
Project description:We hypothesized that preterm spontaneous labor involves aberrant changes in mRNA expression in the placenta. To test this hypothesis, we interrogated the mRNA levels of >50,000 genes and transcript variants using gene expression microarray (Human Genome U133 Plus 2.0 Array, Affymetrix) on 5 placentas collected from preterm spontaneous delivery (<34 weeks of gestation) and another 5 placentas collected from term spontaneous delivery (38-39 weeks). We have identified 229 and 162 genes that were up- or down-regulated, respectively, for more than 3-fold in the preterm placentas compared to the term placentas (Mann-Whitney Rank Sum Test, with multiple testing correction by the Benjamini-Hochberg method, adjusted p-value <= 0.05). Placentas collected from (i) preterm spontaneous delivery (<34 weeks of gestation) and (ii) term spontaneous delivery (38-39 weeks of gestation) were subjected to RNA extraction and hybridization on Affymetrix microarrays. To identify gene expression patterns that are commonly involved in preterm spontaneous labour, we analyzed 5 placentas from each of these 2 groups and tested for any differentially expressed genes by Mann-Whitney Rank Sum Test.
Project description:Preeclampsia (PE), a hypertensive disorder of pregnancy, is hypothesized to be associated with, if not mechanistically related to abnormal placental function. However, the exact mechanisms regulating the pathogenesis of PE remain unclear. While many studies have investigated changes in gene expression in the PE placenta, the role of epigenetics in PE associated placental dysfunction remains unclear. Using the genome-wide Illumina Infinium Methylation 450 BeadChip array, we analyzed gene-specific alterations in DNA methylation in placental biopsies collected from normal pregnant women delivering at term (n=14), with term PE (≥37 weeks; n=19) or with preterm PE (<37 weeks, n=12). Of the 485,582 gene loci on the array, compared to controls, 229 loci were differentially methylated in PE placentas and 3411 loci were differentially methylated in preterm PE (step up p-value <0.05 and >5% methylation difference). Functional annotation of the differentially methylated genes in preterm PE placentas revealed a 32 gene cluster in the cadherin and cell adhesion functional groups (Benjamini p<0.00001). Hypermethylation of CDH11 (p=0.0143), COL5A1 (p=0.0127) and TNF (p=0.0098) and hypomethylation of NCAM1 (p=0.0158) was associated with altered mRNA expression in preterm PE placentas. These studies demonstrate aberrant methylation, correlating with disease severity, in PE placentas. Bisulphite converted DNA from the 45 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2
Project description:Preeclampsia (PE), a hypertensive disorder of pregnancy, is hypothesized to be associated with, if not mechanistically related to abnormal placental function. However, the exact mechanisms regulating the pathogenesis of PE remain unclear. While many studies have investigated changes in gene expression in the PE placenta, the role of epigenetics in PE associated placental dysfunction remains unclear. Using the genome-wide Illumina Infinium Methylation 450 BeadChip array, we analyzed gene-specific alterations in DNA methylation in placental biopsies collected from normal pregnant women delivering at term (n=14), with term PE (≥37 weeks; n=19) or with preterm PE (<37 weeks, n=12). Of the 485,582 gene loci on the array, compared to controls, 229 loci were differentially methylated in PE placentas and 3411 loci were differentially methylated in preterm PE (step up p-value <0.05 and >5% methylation difference). Functional annotation of the differentially methylated genes in preterm PE placentas revealed a 32 gene cluster in the cadherin and cell adhesion functional groups (Benjamini p<0.00001). Hypermethylation of CDH11 (p=0.0143), COL5A1 (p=0.0127) and TNF (p=0.0098) and hypomethylation of NCAM1 (p=0.0158) was associated with altered mRNA expression in preterm PE placentas. These studies demonstrate aberrant methylation, correlating with disease severity, in PE placentas.
Project description:We hypothesized that preterm spontaneous labor involves aberrant changes in mRNA expression in the placenta. To test this hypothesis, we interrogated the mRNA levels of >50,000 genes and transcript variants using gene expression microarray (Human Genome U133 Plus 2.0 Array, Affymetrix) on 5 placentas collected from preterm spontaneous delivery (<34 weeks of gestation) and another 5 placentas collected from term spontaneous delivery (38-39 weeks). We have identified 229 and 162 genes that were up- or down-regulated, respectively, for more than 3-fold in the preterm placentas compared to the term placentas (Mann-Whitney Rank Sum Test, with multiple testing correction by the Benjamini-Hochberg method, adjusted p-value <= 0.05).