Illumina sequencing of vaginal epithelial cells from women using depot medroxyprogesterone acetate or non-hormonal contraception
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE68229 | GEO | 2016/04/23
SECONDARY ACCESSION(S): PRJNA282080
REPOSITORIES: GEO
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Project description:Depot medroxyprogesterone acetate (DMPA) is an injectable hormonal contraceptive used by millions of women worldwide. However, experimental studies have associated DMPA use with genital epithelial barrier disruption and mucosal influx of human immunodeficiency virus (HIV) target cells. We explored the underlying molecular mechanisms of these findings. Ectocervical biopsies and cervicovaginal lavage (CVL) specimens were collected from HIV-seronegative Kenyan sex workers using DMPA (n=32) or regularly cycling controls (n=64). Tissue samples were assessed by RNA-sequencing and quantitative imaging analysis, whereas protein levels were measured in CVL samples. The results suggested a DMPA-associated upregulation of genes involved in immune regulation, including genes associated with cytokine-mediated signaling and neutrophil-mediated immunity. A transcription factor analysis further revealed DMPA-associated upregulation of RELA and NFKB1 which are involved in several immune activation pathways. Several genes significantly downregulated in the DMPA versus the control group were involved in epithelial structure and function, including genes encoding keratins, small proline-rich proteins, and cell-cell adhesion proteins. Pathway analyses indicated DMPA use was associated with immune activation and suppression of epithelium development, including keratinization and cornification processes. The cervicovaginal microbiome composition (Lactobacillus dominant and non-Lactobacillus dominant) had no overall interactional impact on the DMPA associated tissue gene expression. Imaging analysis verified that DMPA use was associated with an impaired epithelial layer as illustrated by staining for the selected epithelial junction proteins E-cadherin, desmoglein-1 and claudin-1. Additional staining for CD4+ cells revealed a more superficial location of these cells in the ectocervical epithelium of DMPA users versus controls. Altered protein levels of SERPINB1 and ITIH2 were further observed in the DMPA group. Identification of specific impaired epithelial barrier structures at the gene expression level, which were verified at the functional level by tissue imaging analysis, illustrates mechanisms by which DMPA adversely may affect the integrity of the genital mucosa.
2022-04-29 | GSE183513 | GEO
Project description:Some evidence suggests that contraceptive use may influence the female genital tract (FGT) mucosal environment. However, comparative analysis of the effects of the most commonly used hormonal and non-hormonal contraceptives on the FGT host gene expression profile have not been evaluated in detail in a randomized clinical trial setting. Among 188 women enrolled in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial (Clinicaltrials.gov ID NCT02550067) between December 2015 and September 2017, we evaluated the effect of three contraceptive methods, injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel (LNG) implant, and a non-hormonal T-380 copper intrauterine contraceptive device (Cu-IUD), on the endocervical host transcriptome at baseline and after one month of randomized contraceptive use, using RNA-Seq transcriptomic analysis.
2023-09-13 | GSE190923 | GEO
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:BACKGROUND:The ECHO trial has relieved apprehension about intramuscular depot medroxyprogesterone acetate (DMPA-IM), however it is still important to understand how DMPA-IM affects the vaginal environment. We sought to describe how DMPA-IM initiation influences vaginal bacteria associated with HIV acquisition in postpartum women. METHODS:Vaginal swabs were collected for Nugent score determination and taxon-specific quantitative PCR of eight bacteria. Enrollment occurred at contraceptive initiation (DMPA-IM or non-hormonal contraception (non-HC)) and repeat vaginal swabs were collected after three months. Generalized estimating equations were used to estimate changes in Nugent score, total bacterial load, and taxa concentrations among contraceptive groups. RESULTS:Women who chose DMPA-IM (n = 33) were more likely to be married (97%vs.67%) and have resumed intercourse since delivery (52%vs.29%) compared to women who chose non-HC (n = 21). After three months, significant decreases in the concentrations of Sneathia species, Mycoplasma hominis, and Parvimonas species Type 1 were seen among non-HC users, however concentrations remained stable among DMPA-IM users; contraceptive method was associated with significantly different changes in M. hominis concentration between groups (p = 0.010). CONCLUSIONS:Our findings suggest that postpartum use of DMPA-IM and non-HC may have differential impacts on the vaginal concentrations of some bacteria that have previously been associated with HIV acquisition.
| S-EPMC7058341 | biostudies-literature
Project description:BackgroundThe vaginal microbiome plays a key role in women's reproductive health. Use of exogenous hormones, such as intramuscular depot medroxyprogesterone acetate (DMPA-IM), may alter the composition of vaginal bacterial community.MethodsVaginal swab samples were collected from postpartum Kenyan women initiating DMPA-IM or nonhormonal contraception (non-HC). Bacterial vaginosis was assessed by Nugent score (Nugent-BV) and bacterial community composition was evaluated using broad-range 16S ribosomal RNA gene polymerase chain reaction with high-throughput sequencing. Changes in Nugent score, alpha diversity (Shannon diversity index), and total bacterial load between contraceptive groups from enrollment to 3 months after initiation were estimated using multivariable linear mixed effects regression.ResultsAmong 54 human immunodeficiency virus-negative women, 33 choosing DMPA-IM and 21 choosing non-HC, Nugent-BV was more common among DMPA-IM users at enrollment. At follow-up, Nugent score had decreased significantly among DMPA-IM users (change, -1.89; 95% confidence interval [CI], -3.53 to -.25; P = .02) while alpha diversity remained stable (0.03; -.24 to .30; P = .83). Conversely, Nugent score remained relatively stable among non-HC users (change, -0.73; 95% CI, -2.18 to .73; P = .33) while alpha diversity decreased (-0.34; -.67 to -.001; P = .05). The total bacterial load decreased slightly in DMPA-IM users and increased slightly among non-HC users, resulting in a significant difference in change between the contraceptive groups (difference, -0.64 log10 gene copies per swab sample; 95% CI, -1.19 to -.08; P = .02). While significant changes in Nugent score and alpha diversity were observed within contraceptive groups, changes between groups were not significantly different.ConclusionsPostpartum vaginal bacterial diversity did not change in DMPA-IM users despite a reduction in Nugent-BV, but it decreased significantly among women using non-HC. Choice of contraception may influence Lactobacillus recovery in postpartum women.
| S-EPMC8204794 | biostudies-literature
Project description:BackgroundDepot medroxyprogesterone acetate (DMPA) has been linked to human immunodeficiency virus type 1 (HIV-1) acquisition.MethodsVaginal microbiota of women using DMPA for up to 2 years were cultured. Mucosal immune cell populations were measured by immunohistological staining.ResultsOver 12 months, the proportion with H2O2-positive lactobacilli decreased (n = 32; 53% vs 27%; P = .03). Median vaginal CD3(+) cells also decreased (n = 15; 355 vs 237 cells/mm(2); P = .03), as did CD3(+)CCR5(+) cells (195 vs 128 cells/mm(2); P = .04), HLA-DR(+) cells (130 vs 96 cells/mm(2); P = .27), and HLA-DR(+)CCR5(+) cells (18 vs 10 cells/mm(2); P = .33).ConclusionsDMPA contraception does not increase vaginal mucosal CCR5(+) HIV target cells but does decrease CD3(+) T lymphocytes and vaginal H2O2-producing lactobacilli.
| S-EPMC4172039 | biostudies-literature
Project description:Vaginal microbiome in response to hormonal contraceptive use
| PRJEB30774 | ENA
Project description:INTRODUCTION:Hormonal contraception with depot medroxyprogesterone acetate (DMPA) may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. In this study, we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on Simian-Human Immunodeficiency Virus (SHIV) acquisition risk in pigtail macaques (Macaca nemestrina). METHODS:Macaques metabolize DMPA faster than humans. We previously identified a per-weight DMPA dose and administration frequency that achieves long-lasting suppression of ovulation in macaques. Eight macaques were given 1.5-mg/kg DMPA monthly, whereas 11 were untreated controls. For comparison, women receive 150 mg (approximately 2 mg/kg) every 3 months. We exposed monkeys to 20 suboptimal SHIV challenges, designed to slowly infect half of controls and allow increased infection in the DMPA group. RESULTS:It took a median 5.5 viral challenges to infect DMPA-treated macaques and 9 challenges for controls (P = 0.27; exact conditional logistic regression). The exact odds ratio was 2.2 (CI: 0.6 to 8.3). Ovulation was suppressed, and the vaginal epithelium was thinned after DMPA treatment in all animals (mean, 30 and 219 mm in DMPA-treated and control macaques, respectively, P = 0.03, t test using the Satterthwaite degrees-of-freedom approximation). CONCLUSIONS:SHIV infections in DMPA-treated macaques were 2.2 times those of controls, but this was not statistically significant. The result is remarkably similar to studies of human DMPA use, which have shown HIV risk increases of a similar magnitude and of variable significance. Taken together with previous studies of higher DMPA doses in macaques, the results suggest a dose-dependent effect of DMPA on Simian Immunodeficiency Virus (SIV) or SHIV acquisition.
| S-EPMC4930010 | biostudies-literature
Project description:BACKGROUND:Depot medroxyprogesterone acetate (DMPA) is associated with HIV acquisition. We studied changes in vaginal microbiota and inflammatory milieu after DMPA initiation. METHODS:In a cohort of HIV-negative Kenyan women, we collected monthly vaginal swabs over 1 year before and after DMPA. Using quantitative polymerase chain reaction, we compared quantities of Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus iners, Gardnerella vaginalis, and total bacterial load (16S ribosomal RNA gene levels). Six vaginal immune mediators were measured with enzyme-linked immunosorbent assay. Trends in the detection and quantity of bacteria were estimated by logistic and linear mixed-effects regression. RESULTS:From 2010 to 2012, 15 HIV-seronegative women initiated DMPA, contributing 85 visits (median, 6 visits/woman; range, 3-8 visits/woman). The median time of DMPA-exposed follow-up was 8.4 months (range, 1.5-11.6 months). Seven women (46%) had bacterial vaginosis within 70 days before DMPA start. L. iners was detected in 13 women (87%) before DMPA start, but other lactobacilli were rarely detected. Gardnerella vaginalis decreased by 0.21 log10 copies per swab per month after DMPA exposure (P = 0.01). Total bacterial load decreased by 0.08 log10 copies per swab per month of DMPA (P = 0.02). Sustained decreases in interleukin (IL)-6 (P = 0.03), IL-8 (P = 0.04), and IL-1 receptor antagonist (P < 0.001) were also noted. Nine women (60%) had L. crispatus detected post-DMPA, which significantly correlated with reduced IL-6 (P < 0.01) and IL-8 (P = 0.02). CONCLUSIONS:Initiation of DMPA led to sustained shifts in vaginal bacterial concentrations and levels of inflammatory mediators. Further studies are warranted to outline components of the vaginal microbiota influenced by DMPA use and impact on HIV susceptibility.
| S-EPMC4770856 | biostudies-literature
Project description:ObjectivesPrior studies suggest that the composition of the vaginal microbiome may positively or negatively affect susceptibility to sexually transmitted infections (STIs) and bacterial vaginosis (BV). Some female hormonal contraceptive methods also appear to positively or negatively influence STI transmission and BV. Therefore, changes in the vaginal microbiome that are associated with different contraceptive methods may explain, in part, effects on STI transmission and BV.Study designWe performed a retrospective study of 16S rRNA gene survey data of vaginal samples from a subset of participants from the Human Vaginal Microbiome Project at Virginia Commonwealth University. The subset included 682 women who reported using a single form of birth control that was condoms, combined oral contraceptives (COCs), depot medroxyprogesterone acetate (DMPA) or the levonorgestrel-releasing intrauterine system (LNG-IUS).ResultsWomen using COCs [adjusted odds ratio (aOR) 0.29, 95% confidence interval (CI) 0.13-0.64] and DMPA (aOR 0.34, 95% CI 0.13-0.89), but not LNG-IUS (aOR 1.55, 95% CI 0.72-3.35), were less likely to be colonized by BV-associated bacteria relative to women who used condoms. Women using COCs (aOR 1.94, 95% CI 1.25-3.02) were more likely to be colonized by beneficial H2O2-producing Lactobacillus species compared with women using condoms, while women using DMPA (aOR 1.09, 95% CI 0.63-1.86) and LNG-IUS (aOR 0.74, 95% CI 0.48-1.15) were not.ConclusionsUse of COCs is significantly associated with increased vaginal colonization by healthy lactobacilli and reduced BV-associated taxa.ImplicationsCOC use may positively influence gynecologic health through an increase in healthy lactobacilli and a decrease in BV-associated bacterial taxa.
| S-EPMC5376524 | biostudies-literature