Project description:Stress urinary incontinence (SUI) greatly affects the daily life of numerous women and is closely related to a history of vaginal delivery and aging. We used vaginal balloon dilation to simulate vaginal birth injury in young and middle-aged rats to produce a SUI animal model, and found that young rats restored urethral structure and function well, but not the middle-aged rats. To identify the characteristics of cellular and molecular changes in the urethral microenvironment during the repair process of SUI. We profiled 51,690 individual female rat urethra cells from 24 and 48 weeks old, with or without simulated vaginal birth injury.
Project description:Background: Vaginal birth causes injury to the pelvic floor and may lead to urinary incontinence. Cell therapy has been proposed to assist in functional recovery. Objective: To assess if intra-arterial injection of mesoangioblasts (MABs) or Vascular Endothelial Growth Factor (VEGF)-overexpressed MABs, improves urethral and vaginal function recovery after simulated vaginal delivery (SVD). Results: All stem-cell injected rats had external urethral sphincteric and vaginal function recovery within 14d, as compared to half of controls. Functional recovery was paralleled by improved muscle regeneration and microvascularization. Recovery was not different between autologous and allogenic MABs. MABsallo-VEGF accelerated functional recovery and increased GAP-43 expression at 7d. We detected early on in the recovery major transcriptional changes in both MABsallo and MABsallo-VEGF. MABSallo upregulated transcripts that encode proteins involved in myogenesis and dendrite development, and downregulated pro-inflammatory processes MABsallo-VEGF upregulated transcripts that encode proteins involved neuron and dendrite development and downregulates genes involved in hypoxia and oxidative stress. 7d after injury, Later MABsallo-VEGF showed a decrease in oxidative and inflammatory response compared to MABSallo treated urethras. These pathways are also downregulated in animals that have recovered at 7d, compared to non-recovered animals. Conclusion: Intra-arterial injection of MABsallo-VEGF enhances neuroregeneration and accelerates functional urethral and vaginal recovery after simulated vaginal delivery. Injection of stem cells induces faster recovery of urethral and vaginal function; cells overexpressing a factor increasing blood vessel formation, were even more effective.
Project description:The study proposes the characterization of the intestinal and vaginal microbiota in long-term radiated cervical and endometrial cancer survivors to study the association with long-term radiotherapy side effects.
Project description:The hormonal contraceptive medroxyprogesterone acetate (MPA) is associated with increased risk of human immunodeficiency virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent scores <7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with decreased levels of estrogen in the plasma, and low vaginal glycogen and α-amylase, factors implicated in vaginal colonization by lactobacilli, bacteria that are believed to protect against STIs. In a humanized mouse model, MPA treatment was associated with low serum estrogen, low glycogen and enhanced HIV-1 susceptibility. The mechanism by which the MPA mediated changes in the vaginal microbiota may contribute to HIV-1 susceptibility in humans appears to be independent of inflammatory cytokines and/or activated T cells. Altogether, these results suggest MPA-induced hypo-estrogenism may alter key metabolic components that are necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota.
Project description:The onset of menopause is accompanied by a dramatic increase in reported symptoms of vaginal dryness, soreness, irritation or itching, pain with intercourse and bleeding after intercourse. Collectively these affect 25-50% of women of post-menopausal age and significantly impact their quality of life. To examine how gene expression differs between these groups, surface vaginal epithelial cells were collected from postmenopausal women suffering from vaginal dryness and appropriate controls not suffering from dryness. Affymetrix GeneChip Human 1.0 ST microarrays were performed on RNA isolated from ten participants.
Project description:The onset of menopause is accompanied by a dramatic increase in reported symptoms of vaginal dryness, soreness, irritation or itching, pain with intercourse and bleeding after intercourse. Collectively these affect 25-50% of women of post-menopausal age and significantly impact their quality of life. To examine how gene expression differs between these groups, surface vaginal epithelial cells were collected from postmenopausal women suffering from vaginal dryness and appropriate controls not suffering from dryness. Affymetrix GeneChip Human 1.0 ST microarrays were performed on RNA isolated from ten participants. Suitable RNA was extracted from ten participants which were classified into two groups, the dryness and control groups, based on diagnosis of dryness by a nurse during gynecoligical examination.