Integrated Analysis of Multiple Microarrays Based on Raw Data Identified Novel Gene Signatures in Recurrent Implantation Failure

Zeng, Hong; Fu, Yu; Shen, Lang; Song, Qisheng

doi:10.3389/fendo.2022.785462

Cited by 8 publications

(6 citation statements)

References 57 publications

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“…GO analysis demonstrated that DEGs in RIF were primarily enriched in lipid metabolism and immune processes. In KEGG analysis, the NF-κB, TNF, and adipocytokine signaling pathways were linked together, which is consistet with similar RIF studies showing dysregulated NF-κB and TNF pathways [ 24 , 38 , 39 , 40 ]. GSEA results demonstrated that RIF was significantly enriched in downregulated graft-versus-host disease, allograft rejection, complement and coagulation cascades, antigen processing and presentation, upregulated fatty acid biosynthesis, ovarian steroidogenesis, and steroid hormone biosynthesis.…”

Section: Discussionmentioning

confidence: 60%

“…RAB32 and TRIB2 had significantly lower expression levels in RIF, whereas NRCAM, PDZD8, ZNF436, HOXB3, SLC25A29, SHROOM3, ATP13A4, and FAM155B expression was significantly upregulated. Notably, in the hub gene analysis, considering that the GSE111974 and GSE92324 datasets came from different platforms and the selection of the RIF cases and control groups in the two datasets was different, we chose to analyze DEGs between the RIF cases and controls in the two datasets separately [ 24 , 25 ], rather than directly merge their original data for analysis [ 26 ]. ROC analyses validated that the hub genes may predict RIF with excellent specificity and sensitivity.…”

Section: Discussionmentioning

confidence: 99%

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Potential Biomarkers and Endometrial Immune Microenvironment in Recurrent Implantation Failure

Gao

et al. 2023

Biomolecules

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The molecular mechanisms underlying unexplained recurrent implantation failure (RIF) remain unclear. This study aimed at identifying potential biomarkers, exploring relevant signaling pathways, and analyzing the contribution of immune cell infiltration in RIF. Microarray expression datasets were extracted from the Gene Expression Omnibus database to perform bioinformatic analyses. The results showed that ten hub genes may predict RIF with high specificity and sensitivity (area under the curve = 1.000). Protein–protein interaction analysis revealed close interactions between the hub genes and the endometrial receptivity array. The real-time quantitative polymerase chain reaction further validated three potential biomarkers (RAB32, TRIB2, and FAM155B). Functional enrichment analyses indicated that immune pathways were significantly downregulated and lipid metabolism pathways were significantly upregulated in RIF compared with the controls. Significant negative correlations were observed between fatty acid biosynthesis and the immune pathways. Immune cell infiltration, including those in CD56dim natural killer, dendritic, Th1, Th2, and regulatory T cells, as well as macrophages, was significantly reduced in RIF compared with the controls used herein. This study may provide a novel perspective on the diagnosis and treatment of RIF.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Potential Biomarkers and Endometrial Immune Microenvironment in Recurrent Implantation Failure

Gao

et al. 2023

Biomolecules

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“…Several previous microarray and bioinformatics studies have addressed gene expression changes related to RIF [10][11][12][13][14][15][16]50] . The advantages of our study are that we carefully reviewed original research and recruited homogeneous samples by excluding known RIF factors.…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis to identify key genes and pathways involved in the endometria of patients with recurrent implantation failure undergoing in vitro fertilization and embryo transfer

Sui

Sun

2023

Reproductive and Developmental Medicine

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Objectives: Recurrent implantation failure (RIF) is a challenging clinical problem that occurs in approximately 10% of patients undergoing in vitro fertilization and embryo transfer. Because of the varied criteria for RIF, as well as differences in the time and methods of endometrial biopsy, previous studies have not reached an agreement regarding the key genes and pathways of RIF. In this study, bioinformatic analyses were performed in a homogeneous population with consistent biopsy conditions to explore the molecular mechanisms and identify key RIF-associated genes and pathways in the endometrium. Methods: Seven datasets from the Gene Expression Omnibus database were reviewed in detail, and GSE111974, GSE103465, and GSE26787 were included for further analysis. Common differentially expressed genes (DEGs) were identified using the GEO2R online tool. Gene Ontology and pathway enrichment analyses were performed and a protein–protein interaction (PPI) network was constructed. The RNA and protein expression files of the hub genes were obtained. Results: A total of 402 common DEGs were identified between patients with RIF and controls. The enrichment of these DEGs was mainly associated with tube morphogenesis, vasculature development, and positive regulation of cell migration. Pathway enrichment indicated that pathways involved in cancer, the vascular endothelial growth factor A-vascular endothelial growth factor receptor 2 signaling pathway, and cell cycle pathways were mainly involved. Moreover, a PPI network was constructed, and the three most significant submodules were mainly involved in rRNA processing and the regulation of proteolysis. The following ten DEGs with high degrees of connectivity were identified as hub genes: CDC42, VEGFA, MAP2K1, APP, CYCS, UBE2I, PLEK, LMNA, SMAD2, and ATRX. Conclusion: Key genes and pathways identified in this study could improve our understanding of the underlying molecular events in RIF and be used as potential biomarkers and therapeutic targets. Further studies are required to confirm these results and explore the functions of hub genes in the endometrium during the implantation window in patients with RIF.

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“…It is up-regulated during the mid-secretory phase in human endometrium and is shown to be lower in HRT patients compared to natural cycles 49 . One of the most strongly expressed genes IDH1 (baseMean 21 840.94) encoding isocitrate dehydrogenase 1, highly expressed in all types of epithelial cells, was 2-fold up-regulated in AMA samples (p adj = 6.15*10-3) (Supplementary File 3) is also a hub gene in RIF 50 . Also, SPDEF encoding SAM pointed domain containing ETS transcription factor, is one of the genes upregulated and HABP2, hyaluronan binding protein 2, is downregulated in patients with recurrent implantation failure 11 .…”

Section: Discussionmentioning

confidence: 99%

Aging affects ciliated cells development in the human endometrial epithelium

Loid

Obukhova

Kask

et al. 2023

Preprint

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The twenties are typically considered the prime reproductive years for women. However, in today’s modern world, many women are choosing to delay family planning, resulting in an increase of females in their forties seeking fertility treatment. Althoughin vitrofertilization (IVF) with donated oocytes and preimplantation genetic testing may help to address the impact of maternal age, the success rate for IVF treatment in this age group is still significantly lower. While endometrial changes, such as abnormal endometrial thickness, inflammatory background, and altered hormone response signaling, are associated with aging, little is known about the molecular features of endometrial aging and their impact on the ability to support embryo implantation. To better understand age-specific changes, we performed endometrial transcriptome profiling of young and advanced age females, undergoing hormonal replacement therapy (HRT) before frozen embryo transfer, followed by immunohistology analysis and single-cell-based deconvolution. Here, we identified 491 differentially expressed genes pointing to the effect of aging on decidualization, cell signaling, inflammation and endometrial receptivity. Our results indicate that p16INK4amay be involved in cellular senescence and the suppression of metabolic and inflammatory processes essential for endometrial preparation for embryo implantation. We have also shown that the proportion of ciliated cells along with ciliary processes is affected by endometrial aging. These findings have important implications for future strategies aimed at improving infertility treatment in women of advanced reproductive age.

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Integrated Analysis of Multiple Microarrays Based on Raw Data Identified Novel Gene Signatures in Recurrent Implantation Failure

Cited by 8 publications

References 57 publications

Potential Biomarkers and Endometrial Immune Microenvironment in Recurrent Implantation Failure

Potential Biomarkers and Endometrial Immune Microenvironment in Recurrent Implantation Failure

Integrated bioinformatics analysis to identify key genes and pathways involved in the endometria of patients with recurrent implantation failure undergoing in vitro fertilization and embryo transfer

Aging affects ciliated cells development in the human endometrial epithelium

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