Loss of endometrial plasticity in recurrent pregnancy loss (RNA-Seq)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE65099 | GEO | 2015/09/16
SECONDARY ACCESSION(S): PRJNA273001
REPOSITORIES: GEO
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Project description:In order to try and identify characteristics of gene expression in the endometrium of women suffering infertility or recurrenty miscarriage, we performed RNAseq on endometrial pipelle biopsies from 20 women. The endometrial transcriptome in the mid-luteal phase of the cycle (window of implantation) is highly divergent in women suffering infertility or miscarriages. 20 mid-luteal endometrial biopsies were analysed from infertile women and patients suffering recurrent pregnancy loss.
2015-09-16 | E-GEOD-65099 | biostudies-arrayexpress
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).
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2010-12-01 | E-MEXP-2942 | biostudies-arrayexpress
Project description:Up to one-tenth of women experience miscarriage in their lifetime. Embryonic aneuploidy is a leading cause of infertility, miscarrage and congenital defects. Here, we identify loss-of-function variants of ELL3, a gene encoding a transcription elongation factor, from couples experienced consecutive early spontaneous miscarriages due to embryonic aneuploidy. Maternal ELL3 knockout leads to oocyte aneuploidy. Furthermore, we found that ELL3 localizes to the spindle during meiosis, and that ELL3 depletion in both mouse and human oocytes increases the incidence of meiotic spindle abnormality. Biochemically, ELL3 competes with TPX2 to interact with the microtubule motor KIF11, promoting its ATP utilization. Live imaging analysis shows that ELL3 is essential for promoting spindle elongation rate and driving chromosome movement. Our findings demonstrate that ELL3 loss-of-function variations could lead to oocyte aneuploidy and early miscarriage.
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Project description:Pregnancy loss is the most common complication of human pregnancy. Recurrent early pregnancy loss (REPL) has multiple etiologies, including endometrial dysregulation leading to “suboptimal” implantation. Although the implantation process is tightly regulated in Eutherian (placental) mammals, the molecular factors contributing to dysregulated endometrial gene expression patterns in women with REPL are largely unknown. We hypothesized that genes that gained novel expression in the endometria of mammals that evolved in the Eutherian stemlineage, coincident with the evolution of pregnancy, are likely essential for establishment and maintenance of normal pregnancy and are, therefore, good candidates for genes whose expression may be dysregulated in disorders such as REPL. To test this hypothesis, we took an evolutionary forward genomics approach to characterize gene expression profiles of midsecretory endometria from women with REPL associated with abnormal endometria based either on histology or molecular expression of cyclin E. We identified 58 genes that were differentially expressed (P<0.001) between women with out-of-phase histological dating vs normal histology, and 81 genes that were differentially expressed (P<0.001) between women with abnormally elevated cyclin E levels vs normal cyclin E. Remarkably, genes that were recruited into endometrial expression during the evolution of pregnancy in Eutherian mammals were significantly enriched for dysregulated genes (P=0.002 for histology, P=0.021 for cyclin E), as well as for immune and signaling pathways with essential roles in endometrial biology. Thus, our novel evolutionary-based forward genomics approach identified genes whose dysregulation during the mid-secretory phase likely contributes to the molecular etiologies of recurrent early pregnancy loss. Total RNA obtained from mid luteal phase endometrium (two replicates per biopsy) from women with recurrent early pregnancy loss (REPL). Endometrial gene expression levels were compared 1) between women with out-of-phase (n=10) and normal histological dating (n=22), 2) between women with abnormally elevated (n=9) and normal (n=23) cyclin E levels. For 5 additional women with abnormally high cyclin E levels, biopsy samples were collected before and after progesterone treatment to investigate the gene expression profiles in response to progesterone.
2014-12-06 | E-GEOD-63901 | biostudies-arrayexpress
Project description:It is estimated that 1% of women suffer from Recurrent Pregnancy Loss (RPL), a debilitating condition currently defined as three or more consecutive miscarriages with no known preventative treatment. However, as 65% of women are able to successfully bear children following diagnosis the risk of RPL appears to be relatively transient. The foundation for embryo implantation is the endometrium – a complex heterogenous tissue that is also transitory in nature, and which dynamically cycles between phases of proliferation, maintenance and elimination. In order to identify biomarkers for the prediction of pregnancy outcome, we generated RNA-seq libraries of 36 endometrial biopsies from women with a quantified pregnancy history. Each biopsy was timed relative to the pre-ovulatory luteinizing hormone surge to coincide with the midluteal implantation window (reported as LH+ for days following the surge), and later associated with the outcome of pregnancy: ‘live birth’, ‘miscarriage’ or ‘ongoing after 12 weeks’. This sample set was anticipated to represent mid-luteal tissues, but observed temporal signatures suggested that this assignment was incorrect. We developed EndoTime as a result of these findings, utilising RT-qPCR expression data for a panel of six temporal marker genes in order to estimate endometrial biopsy timing along a continuous domain.
2021-12-04 | GSE180485 | GEO
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).
2024-06-12 | PXD048340 | Pride
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).
2024-08-27 | PXD048344 | Pride
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.
2016-01-02 | GSE43256 | GEO
Project description:Implantation is dependent on synchronized interactions between the conceptus and surrounding decidual cells but the involvement of clock genes in this process is not well understood. Circadian oscillations are predicated on transcriptional-translational feedback loops, which balance the activities of the transcriptional activators CLOCK and BMAL1 and repressors encoded by PER and CRY genes. Here we show that loss of PER2 expression silences circadian oscillations in decidualizing human endometrial stromal cells (HESCs). Downregulation was preceded by reduced CLOCK binding to a noncanonical E-box enhancer in the PER2 promoter and occurred between 12 - 24 h after exposure to a deciduogenic stimulus. RNA sequencing revealed that premature inhibition of PER2 by siRNA knockdown leads to a grossly disorganised decidual response. Gene ontology analysis highlighted a preponderance of cell cycle regulators amongst the 1,121 genes perturbed upon PER2 knockdown. Congruently, PER2 inhibition abrogated mitotic expansion of differentiating HESCs by inducing cell cycle block at G2/M. Analysis of mid-luteal endometrial biopsies revealed an inverse correlation between PER2 transcript levels and the number of miscarriages in women suffering reproductive failure. Thus, PER2 synchronizes mitotic expansion of HESCs with a periodic decidual gene expression; uncoupling of these events may cause persistent pregnancy failure. Endometrial mRNA profiles of paired control (siRNA-NT) and siRNA-PER2 were generated by deep sequencing, in triplicate using Illumina
2015-09-16 | E-GEOD-62854 | biostudies-arrayexpress