Changes in adipose tissue microRNA expression across the menstrual cycle in regularly menstruating women: a pilot study.
Ontology highlight
ABSTRACT: Cyclical changes in hormone profiles across the menstrual cycle are associated with alterations in metabolic control. MicroRNAs (miRNA) contribute to the regulation of metabolic control, including adipose tissue metabolism. However, the effect of fluctuations in hormonal profile across the menstrual cycle on adipose tissue miRNA expression remain unknown. We used Affymetrux microarray expression analysis to characterise adipose tissue miRNA expression in healthy, regularly menstruating females across the menstrual cycle.
Project description:Repair after damage is essential for tissue homeostasis. Post-menstrual repair of the uterine endometrium is a unique cyclical manifestation of rapid, scar-free, tissue repair taking ~3-5 days. Skin repair post-wounding is slower (~2 weeks) and, in the case of chronic wounds, takes months/years to restore integrity. Herein, the unique ‘rapid-repair’ endometrial environment is translated to the ‘slower-repair’ skin environment. Menstrual fluid (MF), the milieu of post-menstrual endometrial repair, facilitates healing of endometrial and keratinocyte ‘wounds’ in vitro, promoting cellular adhesion and migration, stimulates keratinocyte migration in an ex vivo human skin-reconstruct model and promotes re-epithelialization in an in vivo porcine wound model. Proteomic analysis of MF identified a large number of proteins; several proteins were selected for further investigation, with the endometrium demonstrated as the source of these factors. Functionally, they promote repair of endometrial and keratinocyte wounds by promoting migration, differing significantly from currently available wound-repair treatments, which mainly promote proliferation. Development of these and other menstrual fluid factors into a ‘migration-inducing’ treatment paradigm will provide novel therapies for tissue repair.
Project description:The endometrium undergoes profound progesterone-driven remodeling during the secretory phase of the menstrual cycle in a process called decidualization. In the absence of pregnancy, circulating progesterone levels fall and tissue-wide inflammation and influx of neutrophils precede tissue breakdown and menstrual shedding. These changes are accompanied by wide-scale transcriptomic changes that co-ordinate temporal changes throughout the secretory phase. Here, we sequenced whole endometrial biopsies to identify molecular biomarkers that mark specific stages of the secretory phase, including pre-menstrual tissues. 20 biopsies were timed to specific phases of the secretory cycle based on the donor’s reported LH, the physical morphology of tissues observed via IHC and serum progesterone levels.
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 aim of this research was to determined the plasma miRNA expresion profile in each stage of the endometriosis during menstrual cycle.
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: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:Progress and advancement in assisted reproductive technologies (ART) and its outcomes are limited by the importance of research of endometrial receptivity being overlooked. Due to endometrial biopsy being invasive and in vitro studies lacking reproducibility in vivo, urine is an appealing alternative biofluid source for biomarker research as it can be collected in large quantities non-invasively. The discovery of extracellular vesicles (EVs) in urine (uEVs), has also opened a new avenue in this biomarker research, with these EVs harbouring thousands of proteins that hold promise for biomarker development. In this study urine was collected from human female volunteers and samples representing the different phases of the menstrual cycle were subjected to EV isolation via differential centrifugation and size exclusion chromatography. The resulting uEVs were analysed via Nanoparticle tracking analysis (NTA) to examine the different concentration and size of particles and proteomic analysis performed using shotgun label-free mass spectrometry on the uEV samples and neat urine samples. Our results showed that uEVs were found in numbers depending on the menstrual cycle phase but uEV size was not statistically altered during different stages of the menstrual cycle. Proteomics showed 50% of proteins detected in the neat urine were also present in the uEV samples with 813 proteins were unique in the uEV samples. Proteomics analysis also showed that the menstrual cycle phase affect the uEVs proteomic profile, with some proteins shown to be significantly upregulated and downregulated during the window of implantation phase of the cycle compared to the other non-receptive periods. This data highlights that uEVs characteristics are altered depending on the menstrual cycle phase suggesting the potential of uEVs being used as biomarkers for improving fertility.In this dataset we have the neat urine results.
Project description:The aim of this study was to identify hormonally regulated genes and their related biological pathways in the rhesus macaque cervix during the menstrual cycle. The cervix is the gateway for gamete passage, which is driven by hormonal regulation with progesterone (P) suppressing the passage of gametes. Contraceptives that are progesterone based change the cervix. Progestogen only contraception is reported to act by suppressing ovulation and/or altering cervical mucus secretion. In order to further investigate novel contraceptive targets and their pathways, a microarray was used to discover genes in the cervix that are suppressed under varying lengths of exposure to progesterone throughout an artificial menstrual cycle.