Project description:Asherman’s Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to recurrent surgical removal of intrauterine scarring, which has limited success. Here, we decode the Asherman’s Syndrome endometrial cell niche by analyzing data from over 200,000 cells with single-cell RNA-sequencing in patients with this condition and through in vitro analyses of Asherman’s Syndrome patient-derived endometrial organoids. Our endometrial atlas highlights the loss of the endometrial epithelium, alterations to epithelial differentiation signaling pathways such as Wnt and Notch, and the appearance of characteristic epithelium expressing secretory leukocyte protease inhibitor during the window of implantation. We describe syndrome-associated alterations in cell-to-cell communication and gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, and anti-angiogenic environment.
Project description:Asherman’s Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to recurrent surgical removal of intrauterine scarring, which has limited success. Here, we decode the Asherman’s Syndrome endometrial cell niche by analyzing data from over 200,000 cells with single-cell RNA-sequencing in patients with this condition and through in vitro analyses of Asherman’s Syndrome patient-derived endometrial organoids. Our endometrial atlas highlights the loss of the endometrial epithelium, alterations to epithelial differentiation signaling pathways such as Wnt and Notch, and the appearance of characteristic epithelium expressing secretory leukocyte protease inhibitor during the window of implantation. We describe syndrome-associated alterations in cell-to-cell communication and gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, and anti-angiogenic environment.
Project description:Asherman's Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to recurrent surgical removal of intrauterine scarring, which has limited success. Here, we decode the Asherman's Syndrome endometrial cell niche by analyzing data from over 200,000 cells with single-cell RNA-sequencing in patients with this condition and through in vitro analyses of Asherman's Syndrome patient-derived endometrial organoids. Our endometrial atlas highlights the loss of the endometrial epithelium, alterations to epithelial differentiation signaling pathways such as Wnt and Notch, and the appearance of characteristic epithelium expressing secretory leukocyte protease inhibitor during the window of implantation. We describe syndrome-associated alterations in cell-to-cell communication and gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, and anti-angiogenic environment.
Project description:Given that there is a significant prevalence of Lynch syndrome among patients with endometrial cancer (about 5% of patients with endometrial cancer), and given there is a known risk of endometrial cancer among patients with endometrial hyperplasia (40% risk of pre-existing occult cancer with endometrial intraepithelial neoplasia), it is hypothesized that a diagnosis of endometrial hyperplasia may herald on-going risk of harboring a Lynch Syndrome gene mutation.
The purpose of this study is to examine endometrial hyperplasia specimens and compare the frequency of Lynch Syndrome gene mutations between endometrial hyperplasia and endometrial cancer subjects. This will provide a rationale and opportunity for earlier screening, and reduce colon cancer morbidity and mortality secondary to the Lynch syndrome gene.
Project description:Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies among fertile women. PCOS patients have been confirmed to be accompanied by an increased risk of pregnancy complication, and the exact cause is still unclear. Many factors may cause this situation, and impaired endometrial receptivity could be responsible for adverse pregnancy outcomes in PCOS. Unfortunately, there were still few researches about the molecular mechanisms regarding impaired endometrial receptivity. So we designed this study to explore the secretory endometrial proteome in PCOS patients.
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:Lynch Syndrome increases Endometrial Cancer Occurrence in women due to failure in MisMatch Repair System. Lifetime Cumulative risk of developing endometrial Cancer is approximatively 40% in women with Lynch Syndrome.
Endometrial cancer is the third women cancer in France. Many risk factors are known in general population. Lots of factors are related to over exposure to estrogen.
Data about influence of general risk factors in Women with Lynch Syndrome are poor. Recently, a cohort study appears to have shown a significant decrease in the risk of endometrial cancer with multiparity, the use of hormonal contraception and late menopause in Lynch women. The impact of weight and certain metabolic parameters on the occurrence of endometrial cancers remains poorly known to this day.
Project description:This clinical trial studies universal screening for deoxyribonucleic acid (DNA) mismatch repair deficiency in patients with endometrial cancer, mutations in the genes responsible for Lynch syndrome (inherited forms of endometrial cancers) and other DNA changes that could help guide treatment strategies. Universal tumor DNA sequencing may help doctors better understand how to personalize care, increase length of life, and increase quality of life in patients with endometrial cancer and their relatives.