Genes linked to cervicovaginal integrity are dysregulated in DMPA but not COC contraception users
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ABSTRACT:
PROVIDER: PRJNA433418 | ENA |
REPOSITORIES: ENA
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Project description:Injectable depot medroxyprogesterone acetate (DMPA) is one of the most popular contraception methods in areas of high HIV seroprevalence. Evidence is accumulating that use of DMPA might be associated with an increased risk of acquiring HIV-1; however, mechanisms of this association are not completely understood. We conducted a comparative whole genome transcriptome profiling of human ectocervical tissues before and after use of two hormonal contraception methods: injectable DMPA and not linked to increased risk of HIV acquisition combined oral contraceptive (COC). Microarray analysis identified 235 ectocervical genes altered in the DMPA users. The most striking effect of DMPA, but not COC, was a strong dysregulation of genes strategically involved in the maintenance of epithelial barrier function; the alterations were most likely due to the DMPA-induced estrogen deficiency. We also demonstrated inter-individual heterogeneity in gene expression profiles of the DMPA users that clustered into distinct groups. The differential response may explain divergence in reports on effects of DMPA use. We propose that impairment of the cervicovaginal epithelial integrity in response to DMPA administration is the major mechanism underlying a potential increased risk of HIV-1 acquisition in DMPA users.
2018-04-10 | GSE110313 | GEO
Project description:Cervicovaginal microbiome dysbiosis is associated with increased prevalence and incidence of sexually transmitted infections including HIV. We compared the cervicovaginal proteome as characterised by mass-spectrometry of four groups of African female sex workers (total N=50) grouped by microbiome composition as characterised by 16S rDNA microarray. Group 1 had a Lactobacillus crispatus-dominated microbiome, group 2 a L. iners-dominated microbiome, and groups 3 and 4 had a microbiome containing multiple genera of anaerobic bacteria, with group 3 representing transition to or from dysbiosis and group 4 full dysbiosis. 82 human proteins were differentially abundant among the groups, either showing an increasing or decreasing trend from microbiome groups 1 to 4. Proteins that increased included proteasome subunits and other proteins involved in catabolic metabolism, actin organising proteins and proteins involved in the immune response. Proteins that decreased included antiproteases, keratins, and cornified envelope proteins. We also compared the abundance of pre-defined proteins of interest among microbiome groups: markers of cell type, inflammation, and cell death, and mucins. The dysbiotic groups had increased abundance of proteins unique to lymphocytes and macrophages, pro-inflammatory cytokines, cell death markers, and MUC5B. We conclude that the cervicovaginal human proteome is associated with the cervicovaginal microbiome in a dose-response manner. The changes are likely caused by a pro-inflammatory influx of immune cells and an increase of cell death in dysbiosis. Dysbiosis-associated immune activation, breaches in epithelial integrity, altered mucin balance, and altered protease-antiprotease balance may all contribute to the increased risk of HIV transmission when cervicovaginal dysbiosis is present.
2015-09-25 | PXD001435 | Pride
Project description:Use of hormonal contraceptives (HC) could alter the bacterial community, immune response and epithelial barrier integrity of the female genital tract (FGT) mucosal environment, leading to increased susceptibility to sexually transmitted infections (STIs), including HIV. Here, we tested whether use of three types of HCs, injectable Net-En, combined oral contraceptives (COC) and NuvaRing, a combined contraceptive vaginal ring (CCVR), led to distinct patterns in FGT host transcriptomics transcriptome in South African adolescent females. In an intention-to-treat analysis, we observed few changes in endocervical gene expression in the Net-En and COC groups. Relative to the COC and Net-En arms, samples from the CCVR arm had significant elevation of transcriptional networks driven by IL-6, IL-1 and NFKB, and lower expression of genes supporting epithelial barrier integrity. An integrated multivariate analysis of the cervicovaginal microbiome, transcriptome and cytokines demonstrated that networks of microbial dysbiosis and inflammation accurately discriminated the CCVR arm from the other contraceptive groups, while genes involved in epithelial cell differentiation were predictive of the Net-En and COC arms.
2022-07-11 | GSE171825 | GEO
Project description:Objectives: The aim of this study was to investigate the salivary proteomic profile of smokeless tobacco users in comparison to non-smokers using LC-MS/MS and to investigate the biological changes associated with smokeless tobacco use and oral cancer. Materials & Methods: Saliva samples of 65 participants were collected and divided into three groups: control (25 participants) , smokeless tobacco users group (25 participant), and oral cancer group (15 participant). The mean ages of the control participants, smokeless tobacco users, and oral cancer patients were 37.08 years, 37.8 years, and 52 years, respectively. The saliva samples were then prepared for LC-MS/MS analysis through in-solution digestion. The raw data files were processed using MaxQuant 2.1.0.0 with the human canonical proteome database. Results: The analysis revealed that 343 protein groups exhibited significantly altered abundance in the saliva samples. Among these, 43 out of 51 dysregulated proteins in the smokeless tobacco group were also dysregulated in the oral cancer group. Notably, Apolipoprotein A1 (ApoA1) and Pon1 were found to be significantly increased in both smokeless tobacco users and oral cancer patients. Furthermore, six out of the 20 most significantly altered proteins were mitochondrial proteins, and all of them were decreased relative to controls in both smokeless tobacco users and cancer samples.
2025-11-17 | PXD045926 | Pride
Project description:We performed gene expression analysis using the SCRB-Seq method from cervical and peripheral blood antigen presenting cells that were collected from women with different cervicovaginal bacterial community types.
2015-05-19 | GSE68452 | GEO
Project description:To identify chromatin alterations by host-microbe interactions in cervicovaginal epithelial cells we performed ATAC-sequencing. We identified regions of chromatin that were altered in cervicovaginal epithelial cells after exposure to L. crispatus supernatant.
2023-12-14 | GSE233444 | GEO
Project description:Modification of Gene Expression of Skeletal Muscle in Response to postmenopause with or without Hormone Replacement Therapy. Test samples randomly selected from a larger study in order to verify the validity of microarray experiment. Keywords: time course analysis from HRT users and non-users
2007-11-19 | GSE6378 | GEO
Project description:To elucidate the molecular pathways altered by host-microbe interactions in cervicovaginal epithelial cells we performed whole genome RNA-sequencing. We identified genes and functional pathways that were altered in cervicovaginal epithelial cells after exposure to G. vaginalis or L. crispatus or their supernatant.
2023-12-14 | GSE234836 | GEO
Project description:The cervicovaginal microbiome is a key biological determinant of human immunodeficiency virus (HIV) susceptibility, but its underlying impact on the ectocervical transcriptional landscape is unclear. Ectocervical tissue samples from Kenyan female sex workers were categorized into pre-defined cervicovaginal microbiome groups based on dominant compositions: Lactobacillus crispatus, Lactobacillus iners, Gardnerella, and ‘highly diverse’. The tissue samples (n=21) were assessed using spatial transcriptomics, revealing three epithelial, one mixed border, and nine submucosal gene clusters. Differential gene expression analysis across the microbiome groups and gene clusters identified 3,771 unique genes. The highly diverse microbiome group exhibited the largest differences, mostly located near the epithelial basal membrane, encompassing genes involved in epithelial maintenance, submucosal extracellular matrix structures, and immune function. The L. crispatus- dominated group was identified by genes involved in active immune engagement, supporting mucosal barrier integrity. Weighted gene co-expression analysis confirmed tissue-wide altered gene expression associated with all microbiome groups and with individual bacterial taxa. Despite the assumption that microbiome colonization is restricted to the luminal surface, the transcriptional landscape was affected throughout the mucosa, with the most pronounced effect near both sides of the basal membrane. This broad impact on the mucosal barrier integrity is likely to affect susceptibility to HIV acquisition.
2025-11-25 | GSE300112 | GEO
Project description:Human cervicovaginal microbiome Raw sequence reads
| PRJNA429969 | ENA