Project description:Pre-exposure chemoprophylaxis using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap. Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries. The genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women (20-56 years old) undergoing gynecologic surgeries was measured.
Project description:Pre-exposure chemoprophylaxis using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap. Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries.
Project description:Clinical treatment protocols for infertility with in vitro fertilization-embryo transfer (IVF-ET) provide a unique opportunity to assess the human vaginal microbiome in defined hormonal milieu. Herein, we have investigated the association of circulating ovarian-derived estradiol (E2) and progesterone (P4) concentrations to the vaginal microbiome. Thirty IVF-ET patients were enrolled in this study, after informed consent. Blood was drawn at four time points during the IVF-ET procedure. In addition, if a pregnancy resulted, blood was drawn at 4-to-6 weeks of gestation. The serum concentrations of E2 and P4 were measured. Vaginal swabs were obtained in different hormonal milieu. Two independent genome-based technologies (and the second assayed in two different ways) were employed to identify the vaginal microbes. The vaginal microbiome underwent a transition with a decrease in E2 (and/or a decrease in P4). Novel bacteria were found in the vagina of 33% of the women undergoing IVF-ET. Our approach has enabled the discovery of novel, previously unidentified bacterial species in the human vagina in different hormonal milieu. While the relationship of hormone concentration and vaginal microbes was found to be complex, the data support a shift in the microbiome of the human vagina during IVF-ET therapy using standard protocols. The data also set the foundation for further studies examining correlations between IVF-ET outcome and the vaginal microbiome within a larger study population.
Project description:Streptococcus agalactiae (Group B Streptococcus, GBS) can colonize the human vaginal tract leading to both superficial and serious infections in adults and neonates. To study bacterial colonization of the reproductive tract in a mammalian system, we employed a murine vaginal carriage model. Using RNASeq, the transcriptome of GBS growing in vivo during vaginal carriage was determined. Over one-quarter of the genes in GBS were found to be differentially regulated during in vivo colonization as compared to laboratory cultures. A two-component system (TCS) homologous to the staphylococcal virulence regulator SaeRS was identified as being up-regulated in vivo. One of the SaeRS targets, pbsP, a proposed GBS vaccine candidate, was shown to be important for colonization of the vaginal tract. A component of vaginal lavage fluid acted as a signal to turn on pbsP expression via SaeRS. These data demonstrate the ability to quantify RNA expression directly from the murine vaginal tract and identify novel genes involved in vaginal colonization by GBS. They also provide more information about the regulation of an important virulence and colonization factor of GBS, pbsP, by the TCS SaeRS.
