Project description:The objectives of the study: 1. Does the phase of the menstrual cycle alter microRNA (miRNA) plasma profiles in healthy women of reproductive age and in women with endometriosis? 2. Does this alter prospects for development of a miRNA-based diagnostic test for endometriosis? Prospectively recruited asymptomatic control women and women with surgically diagnosed endometriosis (n = 8 in each group) were included. Each patient provided blood samples in the early proliferative, late proliferative and mid luteal phases of the menstrual cycle (n = 47 total plasma samples). The cycle phase was verified by hormonal profile. RNA was extracted from each sample and expression of microRNAs was assessed using TaqMan Low Density Human miRNA arrays.
Project description:The objectives of the study: 1. Does the phase of the menstrual cycle alter microRNA (miRNA) plasma profiles in healthy women of reproductive age and in women with endometriosis? 2. Does this alter prospects for development of a miRNA-based diagnostic test for endometriosis?
Project description:Natural variability in menstrual cycle length, coupled with rapid changes in endometrial gene expression, makes it difficult to accurately define and compare different stages of the endometrial cycle. We have developed and validated a novel method for precisely determining endometrial cycle stage based on global gene expression. Our ‘molecular staging model’ reveals significant and remarkably synchronized daily changes in expression for over 3,400 endometrial genes throughout the cycle, with the most dramatic changes occurring during the secretory phase.
Project description:To unbiasedly and systematically characterize endometrial transformation across the human menstrual cycle in preparation for embryo implantation, we analyzed the transcriptomic transformation of human endometrium at single cell resolution, dissecting multidimensional cellular heterogeneity of the tissue across the entire natural menstrual cycle.
Project description:The transition of regularly cycling endometrium from the proliferative or Estrogen-dominant phase of the menstrual cycle to the Progesterone-dominant Early and Mid Secretory phases requires wide-spread changes in gene expression that shift the endometrium from a proliferative capacity to a differentiated 'decidual' phenotype in preparation for implantation. This process appears delayed in women with severe endometriosis, suggestive of a progesterone resistant endometrium in this disease. Experiment Overall Design: Endometrial biopsies were obtained from women both with normal endometrial pathologies and no history of endometriosis and from women with laporoscopy proven moderate-severe stage endometriosis. Samples were collected from the Proliferative(PE), Early Secretory (ESE) and Midsecretory (MSE) phases. Samples were then processed for Total RNA isolation and Affymetrix chip hybridization.
Project description:To examine the possibility that biochemical,or molecular signatures of endometrium may prove to be more useful, we have investigated,whole genome molecular phenotyping (54,600 genes/ESTs) of this tissue sampled across the,cycle in 28 normo-ovulatory women, using high-density oligonucleotide microarrays. The results demonstrate,that endometrial samples obtained by two different sampling techniques (biopsy and curetting,hysterectomy specimens) from subjects who are as normal as possible in a human study and,4,including those with unknown histology, can be classified by their molecular signatures and,correspond to known phases of the menstrual cycle with identical results using two independent,analytical methods. Also, the results enable global identification of biological processes and,molecular mechanisms that occur dynamically in the endometrium in the changing steroid,hormone milieu across the menstrual cycle in normo-ovulatory women. The results underscore,the potential of gene expression profiling for developing molecular diagnostics of endometrial,normalcy and abnormalities and identifying molecular targets for therapeutic purposes in,endometrial disorders.
Project description:Human uterine samples were analysed using Visium technology (10X Genomics) to generate a cellular 2D map of the endometrium to study its temporal and spatial changes across the menstrual cycle. Dataset comprises 4 samples from two women in their reproductive age.
Project description:Background: a fundamental challenge for reproductive biology is to understand the menstrual cycle, specially the window of implantation, whose regulation and mechanistic remain incompletely understood in human reproductive physiology. Transcriptomics from a systems biology perspective provides a genomic framework to discover endometrial tissue specific regulation and behavior and its function in reproductive physiology. Results: Here, we applied a transcriptomic analysis of 238 endometrial receptivity related genes using a customized Agilent platform. 507 human endometrial biopsies were analyzed among the menstrual cycle, especially in the expected window of implantation and divided in to transcriptomic profiles using machine learning predictors (SVM and KNN models). The clinical relevance of these profiles was tested defining the best transcriptomic profile for pregnancy and live birth. Weighed Gene Co-expression Networks (WGCN) was applied is these clinically well-defined endometrial states to characterize the gene co-expression tissue specific regulation in humans for pregnancy in comparison with the other transcriptomic stages of menstrual cycle. For the first time, the menstrual cycle has been mapped as a percentage of positive and negative correlations between genes. Thanks to this approach, we have discovered the WOI as the fewest negatively correlated state with the highest proportion of positive correlations (Cochran´s Q = 14324.12, FDR < 2.2e-16) with an average of 84% of positive correlations in pregnant profile, while 53% in the two previous Proliferative (PF) and Early Pre-Receptive profiles and 67% in the late secretory endometrium, just before menstruation renewal. Finally, this study provides a wealth of network data to the scientific community to stimulate hypothesis-driven single-molecule endometrial studies in the form of a user-friendly database called the Menstrual Cycle Gene Co-expression Network (website: www.menstrualcyclegcn.com). Conclusions: this genomic research reveals for first time the pregnant endometrium as a global derepressed state in human menstrual cycle. This indicates the endometrium is generally a repressive tissue in human menstrual cycle with a relaxed WOI period where gene expression reaches the highest proportion of positive correlation, indicating that a decrease of inhibition may allow embryo implantation. Detailed molecular information about co-expression among menstrual cycle is also provided.
Project description:Background: Endometrial organoids are useful tools for studying endometrial biology but are derived from endoemtrial tissue obtained invasively from biopsies and mostly from women not taking hormonal medication. To increase the proportion of women from which endometrial organoids can be obtained, we sought to compare endometrial organoids derived from menstrual fluid and hormone-treated endometrium with standard endometrial organoids. Purpose: To determine if organoids derived from menstrual fluid and hormone-treated endometrium share features with standard endometrial organoids. Methods: RNA sequencing was performed on passage 3 day 7 menstrual fluid organoids (MFO), endometrial organoids from women taking hormonal medication (EMO-H) and standard endometrial organoids (EMO) Results: to determine if organoids derived from menstrual fluid and hormone-treated endometrium share features with staandard endometrial organoids. Conclusions: MFO and EMO-H did not cluster distinctly to EMO, indicating that they share features with EMO and may enable population-wide disease modelling. This is the first publicly available data set demonstrating the transcriptome of EMO-H.
Project description:The fate of the human endometrium is determined during the mid-luteal window of implantation, a crucial period when endometrial stromal cells (EnSCs) differentiate into specialized decidual cells. Upon embryo implantation, these differentiating EnSCs transform the endometrium into the decidua of pregnancy. Conversely, in the absence of pregnancy, decreasing progesterone levels trigger tissue breakdown, leading to menstruation. Despite our understanding of these processes, the precise mechanisms governing this tissue transformation remain elusive. To bridge this knowledge gap, we conducted single-cell RNA sequencing, mapping the transcriptomic profiles of timed endometrial biopsies throughout the luteal phase of the menstrual cycle.