Project description:RATIONALE: The use of intrauterine levonorgestrel may prevent atypical endometrial hyperplasia and endometrial cancer in women with hereditary non-polyposis colorectal cancer or Lynch syndrome. It is not yet known whether intrauterine levonorgestrel and observation are more effective than observation alone in preventing atypical endometrial hyperplasia and endometrial cancer in women with hereditary non-polyposis colorectal cancer or Lynch syndrome.
PURPOSE: This randomized phase III trial is studying intrauterine levonorgestrel and observation to see how well they work compared with observation alone in preventing atypical endometrial hyperplasia and endometrial cancer in women with hereditary non-polyposis colorectal cancer or Lynch syndrome.
Project description:The contraceptive effectiveness of intrauterine devices has been attributed in part to effects of a foreign body reaction on the endometrium. We performed this study to identify compare the effects on the endometrial transcriptome of intrauterine devices and combined oral contraceptives, to better understand their mechanisms of action. We collected endometrial and cervical biopsies from women using the levonorgestrel-intrauterine device, copper intrauterine device or levonorgestrel-containing combined oral contraceptives, and from women not using contraceptives (control group). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. Pathway analysis was performed using EnrichR and Reactome 2016. In endometrial samples from copper intrauterine device users (n=13), there were no genes with statistically significant differential expression compared to controls (n=11), whereas in levonorgestrel-intrauterine device users (n=11), 2509 genes were significantly dysregulated and mapped onto several immune and inflammatory pathways. In combined oral contraceptive users (n=12), 133 genes were significantly dysregulated and mapped predominantly onto pathways involving regulation of metal ions. Both levonorgestrel-intrauterine device and combined oral contraceptive use were associated with significant downregulation of members of the metallothionein gene family. In cervical samples, none of the groups showed statistically significant differential gene expression compared to controls. In conclusion, hormonal and copper intrauterine devices differ significantly in their effects on the endometrial transcriptome, with endometrium from copper intrauterine device users being indistinguishable from luteal phase endometrium. These results suggest that the contraceptive mechanisms of intrauterine devices are unlikely to rely on a common pathway involving a foreign body reaction in the endometrium.
Project description:Intrauterine BoTA treatment has a beneficial effect on vascular reconstruction of functional endometrium prior to embryo implantation by increasing endometrial blood flow near the uterine cavity suggesting BoTA treatment as a potential therapeutic strategy for patients who are suffering from repeated implantation failure with the problems with endometrial receptivity.
Project description:RNA was extracted from the meninges of mice from either Specific pathogen free or Germ free facilities or from the offspring of mice reconstituted with different human microbiomes.
Project description:HuMiChip2 was applied to analyze perform both strain-level identification and the functional profiling of human gut microbiomes from alcoholic cirrhosis patients and healthy individuals with alcohol abuse.
Project description:Intrauterine administration of BoTA might be a potential therapeutic strategy to promote endometrial regeneration via elevation of insulin-like growth factor binding protein 3 mediated osteopontin proteolytic cleavage
Project description:In order to try and identify characteristics of gene expression in the endometrium of women suffering infertility or recurrenty miscarriage, we performed RNAseq on endometrial pipelle biopsies from 20 women. The endometrial transcriptome in the mid-luteal phase of the cycle (window of implantation) is highly divergent in women suffering infertility or miscarriages. 20 mid-luteal endometrial biopsies were analysed from infertile women and patients suffering recurrent pregnancy loss.
