Project description:Using RNA sequencing we show that exposure of M. abscessus to sublethal doses of RIF results in ~25-fold upregulation of Mab_helR; an isogenic deletion mutant of Mab_helR is hypersensitive to RIF and RBT, and over-expression of Mab_helR confers RIF tolerance in M. tuberculosis, implying that Mab_helR constitutes a significant determinant of inducible RIF and RBT resistance.
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:With the rapid development of assisted reproductive techniques (ART), the number and quality of embryos have been optimized, but the embryo implantation rate has not been significantly improved yet. Recurrent implantation failure (RIF), a condition that is typically diagnosed in patients who fail to achieve clinical pregnancy after having undergone at least 3 times of embryo transfers (including a total of ≥4 good-quality embryos), is a challenging problem in ART treatment. Previous studies about RIF are limited to clinical trials and the detection of limited biomarkers within peripheral blood, but few about gene expression within local endometrial tissue and RIF, the key factors involved in RIF remain unclear. Our study was designed with an aim to compare the gene expression profile of RIF women with that of healthy proven fertile controls to explore the influence factors of endometrial receptivity and the mechanisms of RIF.
Project description:Although both of renal interstitial fibrosis (RIF) and renal carcinoma (RCC) are in hypoxic microenvironments, they underwent several contrary pathologicall changes. To investigate the potent targets in the RIF and RCC through transcriptome alterations of hypoxia compared with normoxia, we established hypoxia cell culture models, primarily simulating hypoxia microenvironments in RIF and RCC. By bioinformatics analysis, a certain number of significant differentially expressed genes (DEGs) among RIF and RCC were recognized. We then performed gene expression profiling analysis using data obtained from RNA-seqencing of 2 different cells cultured in hypoxia and normoxia.
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: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: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:Our study is designed to demonstrate altered profiles of circRNAs in the luteal-phase endometrium from patients with RIF. Functional studies will be further confirmed. This study will provide new viewpoint for understanding the roles of non-coding RNA for endometrial stromal cells and epithelial cells function, as well as potential etiologic mechanism for RIF.
Project description:we utilized Exiqon miRCURY™ LNA Array (v18.0, Exiqon, Vedbaek, Denmark) to establish miRNA expression profiles in the endometrial tissues at the time of embryo implantation(day 7 after ovulation) from 8 RIF patients and 10 matched controls. A total of 157 miRNAs exhibited distinct expression patterns in RIF patients as opposed to controls (fold change >2.0 and P-value <0.05).