Dysregulation in Multiple Transcriptomic Endometrial Pathways Is Associated with Recurrent Implantation Failure and Recurrent Early Pregnancy Loss

Abstract

Overlapping disease aetiologies associated with multiple altered biological processes have been identified that change the endometrial function leading to recurrent implantation failure (RIF) and recurrent early pregnancy loss (REPL). We aimed to provide a detailed insight into the nature of the biological malfunction and related pathways of differentially expressed genes in RIF and REPL. Endometrial biopsies were obtained from 9 women experiencing RIF, REPL and control groups. Affymetrix microarray analysis was performed to measure the gene expression level of the endometrial biopsies. Unsupervised clustering of endometrial samples shows scattered distribution of gene expression between the RIF, REPL and control groups. 2556 and 1174 genes (p value < 0.05, Fold change > 1.2) were significantly altered in the endometria of RIF and REPL patients’ group, respectively compared to the control group. Downregulation in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the differentially expressed genes (DEGs) in RIF and REPL including ribosome and oxidative phosphorylation pathways. Gene Ontology (GO) analysis revealed ribosomes and mitochondria inner membrane as the most significantly downregulated cellular component (CC) affected in RIF and REPL. Determination of the dysregulated genes and related biological pathways in RIF and REPL will be key in understanding their molecular pathology and of major importance in addressing diagnosis, prognosis, and treatment issues

Potential Biomarkers and Endometrial Immune Microenvironment in Recurrent Implantation Failure

“…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.…”

The endometrial transcriptome of infertile women with and without implantation failure

“…All women who did not actually undergo a fresh embryo transfer during that cycle ( n = 13) or had a biochemical or clinical pregnancy loss ( n = 9), were excluded from this analysis. The latter were excluded as women with a pregnancy loss may have a different endometrial transcriptome profile from women who had not been able to get pregnant 24 …”

“…The latter were excluded as women with a pregnancy loss may have a different endometrial transcriptome profile from women who had not been able to get pregnant. 24 …”

“…The latter were excluded as women with a pregnancy loss may have a different endometrial transcriptome profile from women who had not been able to get pregnant. 24 In the long-term analysis, we considered the outcome of all IVF/ ICSI cycles within the 12-month follow-up period after enrollment, involving 46 women in total (Figure 1). This includes outcomes after all fresh and frozen embryo transfer cycles.…”

Identification and analysis of biomarkers associated with oxidative stress and ferroptosis in recurrent miscarriage

“…Clarify the differentially expressed genes related downregulation pathways of RM and recurrent implantation failure. [27] We hypothesize that this gene regulates the disease process by participating in these 2 signaling pathways. Multiple connexin proteins are expressed in human tissues, including GJA1, commonly referred to as connexin 43 due to its molecular weight in thousands of daltons, forms GJA1 = connexin 43s and dominates in the decidua and trophoblast.…”