Dataset Information

Comparison of Mucosal Markers of Human Immunodeficiency Virus Susceptibility in Healthy Premenopausal Versus Postmenopausal Women.

ABSTRACT: The objective of this study was to characterize cervicovaginal (CV) mucosal factors modulating susceptibility to human immunodeficiency virus (HIV) acquisition in healthy premenopausal (PRE) and postmenopausal (POST) women before and after treatment with estradiol (E2). We compared CV mucosal epithelial histology and immune cells, vaginal microbiota, antimicrobial activity of and soluble mucosal protein concentrations in the CV fluid lavage (CVL), and p24 antigen production after ex vivo infection of ectocervical tissues with HIV-1BaL among PRE women (n?=?20) in the follicular and luteal phases of the menstrual cycle and POST women (n?=?17) at baseline and after ?1 month of treatment with 0.01% vaginal E2 cream. Compared to PRE women, we measured higher levels of p24 antigen after ex vivo infection in tissues from POST women. POST women had a significantly thinner vaginal epithelium with decreased tight junction proteins and a higher density of mucosal immune T cells and lower levels of CD1a antigen-presenting cells, antimicrobial peptides, and inflammatory cytokines in the CVL (p values <.05). POST women had higher vaginal pH and lower vaginal Lactobacilli (p values <.05) than PRE women. After vaginal E2 therapy, CV endpoints and ex vivo HIV replication in POST tissues were similar to those observed in PRE tissues. The CV mucosa in POST women is thinned and compromised, with increased HIV-target immune cells and decreased antimicrobial factors, being more susceptible to HIV infection. After POST women receive topical E2 treatment, mucosal endpoints are similar to PRE levels.

SUBMITTER: Thurman AR

PROVIDER: S-EPMC5564035 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Comparison of Mucosal Markers of Human Immunodeficiency Virus Susceptibility in Healthy Premenopausal Versus Postmenopausal Women.

Thurman Andrea Ries AR Yousefieh Nazita N Chandra Neelima N Kimble Thomas T Asin Susana S Rollenhagen Christiane C Anderson Sharon M SM Herold Betsy C BC Freiermuth Jamie L JL Starkman Brian S BS Mesquita Pedro M M PMM Richardson-Harman Nicola N Cunningham Tina T Hillier Sharon S Rabe Lorna L Schwartz Jill L JL Doncel Gustavo F GF

AIDS research and human retroviruses 20170516 8

The objective of this study was to characterize cervicovaginal (CV) mucosal factors modulating susceptibility to human immunodeficiency virus (HIV) acquisition in healthy premenopausal (PRE) and postmenopausal (POST) women before and after treatment with estradiol (E2). We compared CV mucosal epithelial histology and immune cells, vaginal microbiota, antimicrobial activity of and soluble mucosal protein concentrations in the CV fluid lavage (CVL), and p24 antigen production after ex vivo infecti ...[more]

PMID: 28398069

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Project description:For decades hormone therapy (HT) has been prescribed to treat the symptoms of menopause, such as vaginal dryness, itching and burning. Here we sought to compare the vaginal microbiomes of postmenopausal women who received low dose estrogen therapy to those of premenopausal and postmenopausal women, and to do so in conjunction with assessing the alleviation of symptoms associated with vaginal atrophy. In this study vaginal swab samples were obtained from 45 women who were classified as either premenopausal, postmenopausal, or postmenopausal and undergoing HT. The vaginal microbiomes of these women were characterized by 16S rRNA gene sequencing and bacterial abundances were quantified by qPCR. We found that the vaginal communities from our cohort could be divided into six clusters (A-F) based on differences in the composition and relative abundances of bacterial taxa. Communities in cluster A were dominated by Lactobacillus crispatus, and those of cluster B were dominated by Gardnerella vaginalis. Communities in cluster C had high proportions of L. iners, while those in cluster D were more even and included several co-dominant taxa. Communities in clusters E and F were dominated by Bifidobacterium and L. gasseri, respectively. The vaginal communities of most postmenopausal women receiving HT (10/15) were dominated by species of lactobacilli and belonged to clusters A, C, and F (P < 0.001). This sharply contrasts with vaginal communities of postmenopausal women without HT, most of which (10/15) were in cluster D, depleted of lactobacilli, and had about 10-fold fewer total bacteria (P < 0.05). The vaginal communities of women in each study group differed in terms of the dominant bacterial species composition and relative abundance. Those of postmenopausal women receiving HT significantly differed from those of postmenopausal women without HT and were most often dominated by species of Lactobacillus. Noteworthy, HT greatly improved vaginal atrophy scores, decreased vaginal pH, and significantly increased bacterial numbers in comparison to postmenopausal women not receiving HT.

Project description:ObjectivesThe purpose of this study was to determine the relationships between uric acid, endothelial function and cardiovascular risk factors and to investigate whether menopausal status was associated with the relationship between uric acid and endothelial function in women.DesignCross-sectional study.Setting3 general hospitals in Japan.Participants749 Japanese women aged 30-74 years recruited from people who underwent health-screening examinations with agreement for measurement of vascular function.MeasuresWe measured serum concentrations of uric acid and flow-mediated vasodilation (FMD). Percentage of FMD (peak diameter-baseline diameter/baseline diameter) was used for analysis. Endothelial dysfunction was defined as FMD ?4.90%, division point for the lowest tertile and the middle tertile of FMD. Menopause women were defined as participants without menstruation for over 1 year or participants with a history of hysterectomy or bilateral oophorectomy.ResultsOf the 749 participants, 368 (49.1%) were premenopausal women and 381 (50.9%) were postmenopausal women. Age, body mass index, systolic blood pressure, total cholesterol, triglycerides, glucose, estimated glomerular filtration rate and Framingham risk score were significantly correlated with serum uric acid level. FMD showed a gradual decrease in accordance with the serum uric acid level in the entire study population (<4 mg/dL, 6.85±3.65%; 4 to <5 mg/dL, 6.79±3.60%; 5 to <6 mg/dL, 6.24±3.58%; ?6 mg/dL, 5.27±3.18%; p=0.01). Multivariate analysis revealed that uric acid was a significantly independent risk factor for endothelial dysfunction in postmenopausal women (OR 1.23, 95% CI 1.01 to 1.50), but not in premenopausal women.ConclusionsThese findings suggest that uric acid can be used as a risk marker of endothelial dysfunction in a female population, and particularly as an independent risk factor in postmenopausal women but not in premenopausal women.Registration number of the studyUMIN000003409.

Dataset Information

Comparison of Mucosal Markers of Human Immunodeficiency Virus Susceptibility in Healthy Premenopausal Versus Postmenopausal Women.

Publications

Comparison of Mucosal Markers of Human Immunodeficiency Virus Susceptibility in Healthy Premenopausal Versus Postmenopausal Women.

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