Project description:StrainFacts accurately quantifies both endogenous and live biotherapeutic product strain abundances in simulated and clinical vaginal microbiota samples
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: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:Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. We interrogated host-pathogen dynamics in a novel murine GDM model of GBS colonization and perinatal transmission. GDM mice had greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing revealed differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM disruption of immunity included reduced uterine natural killer cell activation, impaired recruitment to placentae, and altered vaginal cytokines. Lastly, we observed distinct vaginal microbial taxa associated with GDM status and GBS invasive disease status. Our translational model of GBS perinatal transmission in GDM hosts recapitulates several clinical aspects and enables discovery of host and bacterial drivers of GBS perinatal disease.
