Estradiol-mediated enhancement of the human ectocervical epithelial barrier correlates with desmoglein-1 expression in the follicular menstrual phase
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PROVIDER: PRJNA1143420 | ENA |
REPOSITORIES: ENA
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Project description:Introduction: Structural integrity of the cervical epithelial barrier is crucial for defending the female reproductive tract against sexually transmitted infections, including HIV. Female sex hormones, estradiol and progesterone, play an important role in modulating this epithelial barrier. However, the influence of fluctuating estradiol and progesterone on ectocervical tissue gene and protein expression in naturally cycling women at high risk for sexually transmitted infections is not well understood. Methods: Ectocervical biopsies, cervicovaginal lavage fluid, and venous blood samples were collected from naturally cycling Kenyan female sex workers at two time points, separated by 2 weeks. The first time point represented the luteal phase of the menstrual cycle and the second time point represented the follicular phase. Plasma estradiol and progesterone levels were measured at each time point. Ectocervical tissues were analyzed by RNA-sequencing and in situ immunofluorescence staining. Cervicovaginal lavage samples were evaluated using antibody-based protein profiling. Results: Employing a systems biology approach, we demonstrated that high plasma estradiol levels enhanced ectocervical epithelial integrity. These findings were more pronounced in samples from the follicular phase (when progesterone and estradiol levels were significantly lower) and included increased expression, and more intact distribution, of the desmosomal cadherin DSG1. The effects of progesterone on gene and protein levels, as well as on intact tissue (as visualized by in situ staining), were modest throughout the menstrual cycle. Both estradiol and progesterone levels had limited influence on mucosal immune factors. Conclusion: Estradiol levels were associated with modulation of cervical epithelial barrier integrity, including the expression and distribution of DSG1, during the follicular phase of natural menstrual cycles in Kenyan sex workers.
2025-01-17 | GSE273823 | GEO
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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2024-09-02 | BIOMD0000000494 | BioModels
Project description:Despite extensive studies suggesting increased susceptibility to HIV during the secretory phase of the menstrual cycle, there is limited knowledge of the molecular mechanisms involved. We aimed to explore the ectocervical and endocervical tissue transcriptomes during the proliferative and secretory phases of the cycle using RNA sequencing (RNAseq) to identify potential signatures of susceptibility to HIV. We utilized hysterectomy tissue specimens from subjects not using hormonal contraception/treatment for gynecological conditions. Ectocervical (n=10) and endocervical tissues (n=15) were used for this study. The cycle phase was determined by assessing the histopathology of hematoxylin-and-eosin stained sections of the endometrial mucosa by gynecologic pathologists. Total RNA was isolated from tissues frozen in RNAlater (Ambion) following manufacturer’s instructions (Qiagen RNeasy Fibrous Tissue Mini Kit). After extraction, the quality and the purity of the RNA were measured by the Agilent Bioanalyzer (Agilent, Santa Clara, CA). RNA was labeled and sequenced at the RU Genomics center by using Illumina TruSeq technology (75bp, >30M coverage). The data were analyzed using Ingenuity Pathway Analysis (IPA) software (QIAGEN Inc., https://www.qiagenbioinformatics.com/products/ingenuitypathway-analysis). To inquire into changes in gene expression irrespectively of p-value cut off, pre-ranked genes based on proliferative vs. secretory phase expression were subjected to Gene Set Enrichment Analysis (GSEA) against the Hallmark Gene sets (H) and Immunologic Signatures Gene sets (collection C7) from the Molecular Signatures Database (MSigDB)(http://software.broadinstitute.org/gsea/msigdb/index.jsp). Our data show menstrual cycle phase-associated changes in the transcriptomic landscape of the endocervix and ectocervix, some of which may contribute to changes in HIV susceptibility.
2019-09-25 | GSE122248 | GEO
Project description:We conducted a prospective, open-label study to determine the effect of the NuvaRing on gene expression in the endocervix and immune-related protein expression in cervicovaginal secretions. Women provided endocervical cytobrush samples during the luteal and follicular phases of the menstrual cycle (as determined by progesterone levels) as well as during NuvaRing use. Gene expression was measured using Illumina Human HT12 v4 BeadChip microarrays. We compared the NuvaRing visit to each phase of the menstrual cycle separately, as well as follicular and luteal phase samples to each other, adjusting for technical batch, presence of blood in vaginal discharge, and BV status by Nugent score, and blocking on participant. We found that gene expression in the endocervical canal changed across the menstrual cycle and in response to NuvaRing use. In particular, we observed a continuum of expression of immune-related genes and gene sets in the endocervical canal: highest during NuvaRing use, intermediate in the follicular phase, and lowest in the luteal phase.
2020-12-30 | GSE142058 | GEO
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.
2024-10-27 | GSE246529 | GEO
Project description:Impact of the menstrual cycle and ethinyl estradiol/etonogestrel contraceptive vaginal ring on granulysin and other mucosal immune mediators
| PRJNA595918 | ENA
Project description:The ability to predict the type of tissues or cells from molecular profiles of crime scene samples has practical implications in forensics. In order to identify body fluid-specific DNA methylation changes, genome-wide DNA methylation profiling was carried out for body fluids including menstrual blood and vaginal fluid obtained from 3 female donors aged 19, 27 and 38 years. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in bisulfite converted DNA. Samples included 3 of each vaginal fluid and menstrual bloods collected on the first, second and third days of menstrual bleeding.
2016-05-14 | GSE77283 | GEO
Project description:The ability to predict the type of tissues or cells from molecular profiles of crime scene samples has practical implications in forensics. In order to identify body fluid-specific DNA methylation changes, genome-wide DNA methylation profiling was carried out for body fluids including menstrual blood and vaginal fluid obtained from 3 female donors aged 19, 27 and 38 years. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in bisulfite converted DNA. Samples included 3 of each vaginal fluid and menstrual bloods collected on the first, second and third days of menstrual bleeding. Bisulfite converted DNA from the 12 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2016-05-14 | E-GEOD-77283 | biostudies-arrayexpress
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.
2023-12-04 | PXD047128 | Pride
Project description:Here we developed a novel human induced pluripotent stem cell (hiPSC) model of ARVC to gain insight into the electrical and biomolecular effects of desmoglein-2 (DSG2) mutation in cardiomyocytes. hiPSC-derived cardiomyocytes (hiPSC-CMs) were generated from peripheral blood mononuclear cells donated by an ARVC patient with a pathogenic variant in DSG2, c.2358delA.
2021-06-06 | GSE176209 | GEO