Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA128681 | ENA |
REPOSITORIES: ENA
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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
Project description:Recurrent miscarriage (RM) is the occurrence of repeated pregnancies that end in miscarriage of the fetus before 20 weeks of gestation. Recurrent miscarriages affect about 1-2% of couples trying to conceive; however, mechanisms leading to this complication are largely unknown. Our previous studies using comparative proteomics identified 314 differentially expressed proteins (DEPs) in placental villous. In this study, we identified 5479 proteins from a total of 34157 peptides in decidua of patients with early recurrent miscarriage. Further analysis identified 311 DEPs in the decidua tissue; 159 proteins showed the increased expression while 152 proteins showed decreased expression. These 311 proteins were further analyzed using Ingenuity Pathway Analysis (IPA). The results suggested that 50 DEPs could play important roles in the embryonic development. Furthermore, network analysis of the placental villous and decidua embryonic development DEPs was performed in STRING database to find the core gene. This study identifies several proteins that are specifically associated with embryonic development in decidua of patients with early recurrent miscarriage, these results provide new insights into potential biological mechanisms and may ultimately inform recurrent miscarriage.
2021-07-30 | PXD023849 | 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. 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
Project description:Maternal-fetal interface plays a crucial role to ensure a successful pregnancy. RM (≥3 consecutive pregnancy losses) occurring in 1-3% of fertile couples has a heterogeneous background with contribution from both genetic and environmental factors. As several physiological processes are affected in the pathogenesis of RM, it serves as a good model to study the processes at the maternal-fetal interface. We aimed to map differentially expressed genes and pathways affected in case of RM. Affymetrix® GeneChip® HG-U133 Plus 2.0 Array was applied to placental tissue from 4 RM cases (mean gestational age 63 days) and 6 elective abortions as controls (mean gestational age 62.8 days). Between the two groups 30 transcripts representing 27 genes showed differential expression. 10 genes with the highest fold-change were chosen for validation and further replicated in an independent sample set (9 RM cases, 17 controls) using Taqman® RT-qPCR. RM patients exhibited significant upregulation of two genes: apoptosis inducing ligand TRAIL (p=1.4x10-3) and S100A8 (p=7.9x10-4), encoding for inflammatory marker calprotectin. Combinatory effect of TRAIL, S100A8 and ASMTL provided a highly sensitive test distinguishing RM cases from controls (ROC analysis, area under curve=0.967). Immunohistochemical staining detected TRAIL and ASMTL mainly in trophoblastic cells and S100A8 in myeloid cells of maternal blood at maternal-fetal interface of first trimester placenta. In conclusion, genome wide expression profiling distinguished three differentially expressed genes in RM placentas: TRAIL, S100A8 and ASMTL. Although the detected gene expression alterations related to various pathways could be primary (causing) or secondary (consequence) events associated with the process of RM, the joint contribution of identified markers may provide a highly predictive test for detection of early pregnancy complications 10 gene arrays, 6 in control group and 4 in cases
2010-12-31 | E-GEOD-22490 | biostudies-arrayexpress
Project description:To further analyze the change of microRNA (miRNA) between TRAIL-sensitive and TRAIL-resistant Bel-7402 cells Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
2015-10-20 | GSE74130 | GEO
Project description:Antiphospholipid antibodies, a maternal risk factor for preeclampsia, increase shedding of necrotic trophoblast debris from the placenta, leading to endothelial dysfunction. Using Affymetrix HGU133 Plus 2 microarrays, we found changes in the transcriptome of placental explants treated with antiphospholipid antibodies including seven mRNAs encoding for genes BCL2L1, MCL1, PDCD2L, FASLG, SEMA6A, PRKCE and TRAIL that are involved in the regulation of apoptosis. Quantitative real-time RT-PCR and immunohistochemistry confirmed a reduction in TRAIL expression. These results may help to understand how antiphospholipid antibodies affect trophoblast cell death and how the antibodies could contribute to the pathogenesis of preeclampsia. Three different first-trimester placentas (8-8.5 weeks gestation) were dissected into 6 explants each and cultured either with antiphospholipid antibodies (25ug/mL) or untreated media for 16h. RNA was extracted from treated placental explants and Affymetrix HGU133 Plus 2 arrays were conducted to investigate changes in mRNA expression. Untreated: 1UNT, 2UNT, 3UNT Antiphospholipid antibody treatment: 1APL, 2APL, 3APL Biological replicates: 1, 2, 3
2012-02-27 | E-GEOD-36083 | biostudies-arrayexpress
Project description:Antiphospholipid antibodies, a maternal risk factor for preeclampsia, increase shedding of necrotic trophoblast debris from the placenta, leading to endothelial dysfunction. Using Affymetrix HGU133 Plus 2 microarrays, we found changes in the transcriptome of placental explants treated with antiphospholipid antibodies including seven mRNAs encoding for genes BCL2L1, MCL1, PDCD2L, FASLG, SEMA6A, PRKCE and TRAIL that are involved in the regulation of apoptosis. Quantitative real-time RT-PCR and immunohistochemistry confirmed a reduction in TRAIL expression. These results may help to understand how antiphospholipid antibodies affect trophoblast cell death and how the antibodies could contribute to the pathogenesis of preeclampsia.
2012-02-27 | GSE36083 | GEO
Project description:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a well-known inducer of apoptosis via formation of the primary death-inducing signaling complex (TRAIL-DISC) at the level of membrane death receptors (DR4 and DR5) which recruit successively FADD and caspase-8. TRAIL can also induce necroptosis when caspases are inhibited. Necroptosis is a regulated cell death dependent on the formation of a cytosolic necrosome complex which includes RIPK1, RIPK3 and MLKL proteins. Elucidating the molecular mechanisms involved in TRAIL-induced necroptosis might provide new insights into the TRAIL death signaling pathway. Here, we report the analysis by mass spectrometry of endogenous RIPK3-dependent necrosome complex constituents upon necroptosis induced by TRAIL/z-VAD/Birinapant (TzB) in HT29 cells. Besides characterization of RIPK1, RIPK3, MLKL, FADD, caspase-8, we find TRIM21 as a new constituent of the necrosome complex. Moreover RIPK1, RIPK3, MLKL, P-MLKL, FADD, caspase-8 and TRIM21 are also found associated to the native TRAIL-DISC upon TzB stimulation showing initiation of the necrotic pathway at the level of TRAIL death receptors in HT29 cells. Finally, TRIM21 may positively modulate necroptosis induction by downregulating NF-kB activation.
2021-03-18 | PXD003383 | Pride
Project description:YY1 is a sequence-specific DNA-binding transcription factor that has many important biological roles. However, its function in trophoblasts at the maternal-foetal interface remains to be elucidated. In this study, we used an mRNA microarray and quantitative reverse transcription-PCR and compared the YY1 mRNA expression level in trophoblasts between patients with recurrent miscarriage (RM) and healthy control subjects. Our results revealed that YY1 mRNA expression was significantly lower in the trophoblasts of the RM group compared with the healthy control group. Furthermore, immunofluorescence and immunohistochemical data showed that YY1 was highly expressed in human placental villi during early pregnancy, especially in cytotrophoblast cells and invasive extravillous trophoblasts, and it was expressed at a much lower level in the placental villi of term pregnancy. YY1 overexpression enhanced the invasion and proliferation of trophoblasts, while knockdown of YY1 repressed these effects. Antibody array screening revealed that YY1 significantly promoted MMP2 expression in trophoblasts. Bioinformatics analysis identified three YY1-binding sites in the MMP2 promoter region, and chromatin immunoprecipitation analysis verified that YY1 binds directly to its promoter region. Importantly, inhibition of YY1 by siRNA clearly decreased trophoblast invasion in an ex vivo explant culture model. Overall, our findings revealed a new regulatory pathway of YY1/MMP2 in trophoblast cells invasion during early pregnancy, and indicated that YY1 may be involved in the pathogenesis of RM. Total RNA was isolated using Trizol from trophoblast cells from three healthy controls (HC) and three recurrent miscarriage (RM) patients. Total RNA were extracted and used for hybridizing Affymetrix chips (GeneChip® Human Transcriptome Array 2.0(HTA2.0)). Data were normalised by gcRMA method and raw p-values adjusted by Bonferroni procedure (1%).
2016-01-21 | E-GEOD-76862 | biostudies-arrayexpress
Project description:To identify intrinsic mechanismis that mediating Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance , gene expression analysis was performed on MDA-MB-231 cell lines exposed to TRAIL, in parental (Sensitive) or treat to resistance (TTR) conditions.
2017-05-29 | GSE82047 | GEO