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.
Project description: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: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:Roblitz2013 - Menstrual Cycle following GnRH analogue administration
The model describes the menstrual cycle feedback mechanisms. GnRH, FSH, LH, E2, P4, inbibins A and B, and follicular development are modelled. The model predicts hormonal changes following GnRH analogue administration. Simulation results agree with measurements of hormone blood concentrations. The model gives insight into mechanisms underlying gonadotropin supression.
This model is described in the article:
A mathematical model of the human menstrual cycle for the administration of GnRH analogues.
Röblitz S, Stötzel C, Deuflhard P, Jones HM, Azulay DO, van der Graaf PH, Martin SW.
J. Theor. Biol. 2013 Mar; 321: 8-27
Abstract:
The paper presents a differential equation model for the feedback mechanisms between gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), development of follicles and corpus luteum, and the production of estradiol (E2), progesterone (P4), inhibin A (IhA), and inhibin B (IhB) during the female menstrual cycle. Compared to earlier human cycle models, there are three important differences: The model presented here (a) does not involve any delay equations, (b) is based on a deterministic modeling of the GnRH pulse pattern, and (c) contains less differential equations and less parameters. These differences allow for a faster simulation and parameter identification. The focus is on modeling GnRH-receptor binding, in particular, by inclusion of a pharmacokinetic/pharmacodynamic (PK/PD) model for a GnRH agonist, Nafarelin, and a GnRH antagonist, Cetrorelix, into the menstrual cycle model. The final mathematical model describes the hormone profiles (LH, FSH, P4, E2) throughout the menstrual cycle of 12 healthy women. It correctly predicts hormonal changes following single and multiple dose administration of Nafarelin or Cetrorelix at different stages in the cycle.
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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 goal of this study was to identify genes differentially expressed in the follicular and luteal phases of the menstrual cycle in the human endocervix and to identify significantly represented biological pathways and processes. This was done in order to better understand mechanisms associated with hormonal regulation of endocervix function which has implications in susceptibility to infections.
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:Current endometrial receptivity tests require an invasive method of collecting of endometrial biopsies that can cause general discomfort and adverse events such as infections, pain, and bleeding. Therefore, minimally-invasive methodologies for receptivity evaluation are needed. Cervical cells could offer a great potential for endometrial receptivity testing because cervical cell collection by cytobrush is a standardized, quick, simple, well tolerated, minimally invasive and routinely used sampling technique in everyday gynaecological practice. To date, no studies have evaluated the suitability of cervical cells for endometrial receptivity testing based on transcriptional profiling throughout the menstrual cycle. In this study, paired samples of the endometrium and cervical cells were obtained from 20 women in different menstrual cycle time-points in natural cycles and women undergoing hormonal replacement cycles. The gene expression profiles of cervical cells showed no apparent clustering according to their collection time and menstrual cycle phase. Transcriptome analysis identified only four (KIF2C, CENPF, HLA-DRB5 and CUTALP) differentially expressed genes between the early- and mid-secretory samples, suggesting that the transcriptomes of cervical cells, in contrast to endometrial tissue, do not exhibit significant differences during the window of implantation opening. The largest differences in the transcriptome of cervical cells were noticed in late-secretory phase, before initiation of menstruation. The results of our study suggested that cervical cells’ transcriptome does not reflect the gene expression pattern of endometrial tissue during the WOI and these cells offer little or no potential for endometrial receptivity diagnostics.
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: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.