Endometrial Tissue RNA expression in Recurrent Implantation Failure vs. Conrol
Ontology highlight
ABSTRACT: We aimed to identify altered biological processes in the endometrium that may be potential markers of receptive endometrium. RNA expression profiling of the endometrium during the window of implantation was performed in patients with Recurrent Implantation Failure (RIF) versus fertile controls.
Project description:Transcriptome profile of receptive phase endometrium among infertile women with recurrent implantation failure (RIF) in two different endometrial preparation protocols for FET was analyzed: natural cycle (NC-FET) vs. artificial cycle (AC-FET). Fifteen endometrial biopsy samples were obtained: women with unexplained RIF (n = 5) in natural cycles for FET (NC-FET), women with unexplained RIF undergoing artificial endometrial preparation (n = 5) for FET (AC-FET), and healthy women (n = 5) with proven fertility in natural cycles (NC-FC) (Control group). All endometrial biopsies were obtained during the mid-secretory phase, at the time of ‘window of implantation’.
Project description:Transcriptome profile of receptive phase endometrium among infertile women with recurrent implantation failure (RIF) in two different endometrial preparation protocols for FET was analyzed: natural cycle (NC-FET) vs. artificial cycle (AC-FET). Fifteen endometrial biopsy samples were obtained: women with unexplained RIF (n = 5) in natural cycles for FET (NC-FET), women with unexplained RIF undergoing artificial endometrial preparation (n = 5) for FET (AC-FET), and healthy women (n = 5) with proven fertility in natural cycles (NC-FC) (Control group). All endometrial biopsies were obtained during the mid-secretory phase, at the time of ‘window of implantation’.
Project description:To compare the lncRNA expression profile of RIF (recurrent implantation failure) and normal control endometrium,endometrium samples were collected at window of implantation (LH+6~10 days) The dysregulated lncRNAs between RIF and control group were deem to be involve in the regulation of endometrium receptivity
Project description:The molecular mechanisms underlying window of implantation (WOI) displacement in patients with recurrent implantation failure (RIF) remain unclear. This study aims to explore the transcriptomic signatures of endometrium with normal and displaced WOIs during HRT cycles and to identify the causes of endometrial receptivity (ER) abnormalities and WOI displacement in RIF patients. 40 RIF patients were recruited and underwent personalized embryo transfer (pET) guided by the predicted results of endometrial receptivity diagnosis (ERD) model. Transcriptome analysis of endometrium from patients with clinical pregnancies after pET was performed to identify differentially expressed genes (DEGs) associated with WOI displacement. The ERD results indicated that 67.5% of RIF patients (27/40) were non-receptive in the conventional WOI (P+5) of the HRT cycle. The clinical pregnancy rate in RIF patients improved to 65% (26/40) after ERD-guided pET, indicating the effectiveness of transcriptome-based WOI prediction. Among the 26 patients with clinical pregnancy, the gene expression profiles of P+5 endometrium from advanced (n=6), normal (n=10) and delayed (n=10) WOI groups were significantly different from each other. 10 DEGs (CES4A, LRRC1, SLC25A48, TM4SF4, DPP4, CXCR1, CXCR2, OSM, LCN2 and TNFRSF10C ) identified among P+5 endometrium of 3 groups were involved in immunomodulation, transmembrane transport and tissue regeneration, which could accurately classify the endometrium with different WOIs.
Project description:Endometrial receptivity is imperative to achieving pregnancy in humans. A disruption in the development of endometrial receptivity is responsible for recurrent implantation failures (RIF) of endometrial origin. To further understand the molecular mechanisms behind the endometrial receptivity process, we used the 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) method to compare and quantify the proteomes from endometrial biopsies of three different endometrial statuses (fertile women, IUD carriers and RIF patients). Overall, iTRAQ allowed to identify 1,889 non-redundant proteins. Of these, 188 were differentially expressed proteins (DEP) (p-value < 0.05) among the three endometrial groups. Pairwise comparisons revealed 133 significant DEP in fertile vs. IUD carriers and 158 DEP in RIF vs. IUD carriers. However, no DEP were identified between fertile and RIF patients. Western blot validation of three DEP involved in endometrial receptivity (Plastin 2, Lactotrasferrin, and Lysozyme) confirmed our iTRAQ results. Moreover, functional KEGG enrichment revealed that complement and coagulation cascades and peroxisome were the two most significant pathways for the RIF vs. IUD comparison and ribosome and spliceosome for the fertile vs. IUD comparison, as possible important pathways involved in the endometrial receptivity acquisition. Our findings confirm that an IUD introduces numerous changes in the endometrial protein profile when compared to fertile and RIF endometria, revealing some key proteins involved in endometrial receptivity. The lack of DEP between fertile and RIF patient endometria suggest either that idiopathic RIF may not have an endometrial origin, with other as-yet-unknown factors involved.
Project description:Transcriptomic studies have identified gene expression profiles characteristic of the window of implantation and preliminary studies have indicated that these may be disrupted in some women with recurrent implantation failure (RIF). The aims of this study were to elucidate how the endometrial gene expression profile differs between women with RIF and controls, and to investigate whether a predictor set of genes could be identified able to distinguish between these women.
Project description:The objective of the study was to compare the microRNA content in uterine fluid from patients with recurrent implantation failure (RIF) to that of healthy fertile women. It is a descriptive laboratory study including healthy fertile women and patients with RIF, defined as three failed in vitro fertilization cycles with high quality embryos. Study subjects were instructed to monitor their menstrual cycles using a luteinizing hormone test kit. Uterine fluid was collected on day LH+ 7-9 by flushing with saline. Samples were processed for small RNA sequencing and results were analysed using bioinformatics. The main outcome measure was to identify differentially expressed miRNAs between patients with RIF and healthy fertile women.
Project description:Despite great advances in assisted reproductive technology (ART), unexplained recurrent implantation failure (RIF) due to disorder of endometrial receptivity still cannot be effectively avoided. More importantly, cell characteristics and cell communication that regulate endometrial receptivity and differentiation, and its disorders in RIF at the window of implantation (WOI) remain rudimentary. Here we characterized the transcriptomes of four major cells in human endometrium from healthy control and RIF patients at single-cell resolution. We discovered the dynamic change characteristics of four major endometrial fibroblast-like cells with different endometrial receptivity, reported a novel pluripotent endometrial glandular epithelial cell with high levels of progesterone receptor and exosomes, and defined a unique ITGA1+CXCR4+ NK cell for connecting endometrial nonimmune cells and immune cell infiltration at the WOI. Additionally, we developed a systematic repository of cell-cell communication for endometrial differentiation and the opening of endometrial receptivity via the ligand-receptor complexes interactions. Our study provides deeper insights into aberrant molecular and cellular characterizations, and the endometrial microenvironmental disorders of RIF patients that are potentially applicable to improve the etiological diagnosis and therapeutics of unexplained RIF.
Project description:Recurrent implantation failure (RIF) is a challenge in the field of reproductive medicine. The dysfunction of endometrium is one of the pathogenesis of implantation failure. We used microarrays to detail the global programme of gene expression underlying the molecular pathogenesis of implantation failure.
Project description:Patient-control group project investigating recurrent failure of embryo-implantation by expression analysis of endometrium biopsies