Differentially expressed mRNA transcripts in the placenta delivered by preterm versus term spontaneous labour
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ABSTRACT: 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).
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:Differentially expressed mRNA transcripts in the placenta delivered by term spontaneous labour compared to those delivered by elective term cesarean section. We hypothesized that the labour process involves 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 term spontaneous delivery and another 5 placentas collected from elective term cesarean delivery. To minimize the effect of gestational age on gene expression, these two groups of placentas were matched for their gestational ages at delivery. We have identified 134 and 128 genes that were up- or down-regulated, respectively, for more than 3-fold in the term (spontaneous) labour placentas compared to the term (elective) cesarean placentas (Mann-Whitney Rank Sum Test, p-value <= 0.05 after Benjamini and Hochberg adjustment for multiple testing).
Project description:Differentially expressed mRNA transcripts in the placenta delivered by term spontaneous labour compared to those delivered by elective term cesarean section. We hypothesized that the labour process involves 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 term spontaneous delivery and another 5 placentas collected from elective term cesarean delivery. To minimize the effect of gestational age on gene expression, these two groups of placentas were matched for their gestational ages at delivery. We have identified 134 and 128 genes that were up- or down-regulated, respectively, for more than 3-fold in the term (spontaneous) labour placentas compared to the term (elective) cesarean placentas (Mann-Whitney Rank Sum Test, p-value <= 0.05 after Benjamini and Hochberg adjustment for multiple testing). Experiment Overall Design: Placentas collected from (i) term spontaeous labour and (ii) elective term cesarean section were subjected to RNA extraction and hybridization on Affymetrix microarrays. To identify gene expression patterns that are commonly involved in term spontaneous labour, we analyzed 5 placentas from each of these 2 groups and tested for any differentially expressed genes by non-parametric statistical methods.
Project description:The project aimed to determine proteomics changes in decidua from patients suffering from unexplained early recurrent pregnancy loss (RPL) compared to women undergoing elective abortions. Comparative proteomics analysis by label-free data-independent LC-MS/MS was performed on fresh frozen decidua tissues from 19 RPL patients and 10 controls. Samples from EPL patients were preselected to include only patients with 2 or more recurrent pregnancy losses (RPL), no previous live birth, gestational week from 6-10 weeks and excluded fetal chromosomal abnormalities. Control samples were from women without history of previous miscarriage, ectopic pregnancy or preterm delivery, with at least one live born child, at 6-10 gestational weeks and without fetal chromosomal abnormalities. Patients and controls had no significant differences regarding age (Median age RPL = 30; Median age Controls = 34; Mann–Whitney U-test p = 0.082). The mean gestational weak (GW) was 7.9±1.0 weeks in the RPL group and 8.3±1.2 weeks in the control group, without statistically significant difference between groups (Median GW RPL = 8; Median GW Controls = 8; Mann–Whitney U-test p = 0.361).
Project description:The project aimed to determine proteomics changes in chorionic villi from patients suffering from unexplained early recurrent pregnancy loss (RPL) compared to women undergoing elective abortions. Comparative proteomics analysis by label-free data-independent LC-MS/MS was performed on fresh frozen chorionic villi from 13 RPL patients and 10 controls. Samples from EPL patients were preselected to include only patients with 2 or more recurrent pregnancy losses (RPL), no previous live birth, gestational week from 6-10 weeks and excluded fetal chromosomal abnormalities. Control samples were from women without history of previous miscarriage, ectopic pregnancy or preterm delivery, with at least one live born child, at 6-10 gestational weeks and without fetal chromosomal abnormalities. Patients and controls were between 24-44 years with no significant differences among groups regarding age (Median age RPL = 29; Median age Controls = 34; Mann–Whitney U-test p = 0.078). The mean gestational weak (GW) was 7.9±0.8 weeks in the RPL group and 8.3±1.2 weeks in the control group, without statistically significant difference between groups (Median GW RPL = 8; Median GW Controls = 8; Mann–Whitney U-test p = 0.484).
Project description:Placental insufficiency is implicated in spontaneous preterm birth (SPTB). We performed RNA-seq study in male and female placentas from women (African American, self-identified) with SPTB (< 36 weeks gestation) compared to normal pregnancies (≥ 38 weeks gestation) to assess the alterations in gene expression profiles.
Project description:Comparing miRNAs expression levels in chorioamniotic membranes from women at term in labor (TL), women at term not in labor (TNL) and women who deliverd preterm (PTLC). The goal was to see if miRNA levels are indicators of preterm delivery or spontaneous labor at term. A two-channel technology was used in this experiment in which a pooled reference RNA was used for competitive hybridization. The pooled reference was generated at Exiqon in Denmark from a mixture of several human tissues (placenta, thyroid, brain, adipose, spleen, liver, colon, skeletal muscle, ovary, kidney, heart, cervix, testes, esophagus, small intestine, prostate, trachea, thymus, bladder, lung).
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:Preterm birth, defined as delivery before the 37th week of gestation, is the most common cause of neonatal mortality and the second leading cause of death in children under five years of age. Preterm birth is associated with immediate and long term morbidity as well as growth and developmental delay. Currently there is no treatment that can prevent or block preterm labor. In order to identify the molecular regulators of preterm spontaneous labor in the human myometrium, we studied the gene expression profiles of samples with Preterm Spontaneous Labour (PSL) and compared them with the gene expression profiles of samples with Preterm No Labor (PNL).