Project description:A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. A Nugent scoring system serves as a proxy for determining the ratio of lactobacilli to other vaginal inhabitants where a high score usually represents a diseased state, whilst an intermediate score represents a warning zone. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate score, the effect of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 on the microbiota and host response. The probiotic treatment did not result in changes to clinical parameters such as dryness, irritation and comfort, compared to when placebo was applied. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the proportional abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response and multiplex cytokine analysis showed up-regulation of IL-5. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle trigger molecular changes induced by the host to instillation of probiotic strains. A total of 35 total RNA samples extracted from vaginal brushes were analyzed on Affymetrix Gene 2.0 ST arrays from 14 Participants collected over multiple visits including administration of either a probiotic supplement or placebo control.
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:A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. A Nugent scoring system serves as a proxy for determining the ratio of lactobacilli to other vaginal inhabitants where a high score usually represents a diseased state, whilst an intermediate score represents a warning zone. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate score, the effect of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 on the microbiota and host response. The probiotic treatment did not result in changes to clinical parameters such as dryness, irritation and comfort, compared to when placebo was applied. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the proportional abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response and multiplex cytokine analysis showed up-regulation of IL-5. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle trigger molecular changes induced by the host to instillation of probiotic strains.
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.
Project description:Women’s aging is characterized by menopausal loss of ovarian function, which has been suggested as a contributing factor to aging-related muscle deterioration and predisposes to the metabolic dysfunctions. However, the underlying molecular mechanisms have remained unknown. To identify mechanisms, we utilized muscle samples from 24 pre- and postmenopausal women, established proteome-wide profiles and identified upstream regulators and downstream cellular pathways associated with the differences in age, menopausal status and use of hormone replacement therapy (HRT). None of the premenopausal women used hormonal medication while the postmenopausal women were monozygotic twin-sister pairs who were either current HRT users or had never used HRT. The proteomic analyses resulted in the quantification of 762 muscle proteins of which 158 were for the first time associated with female muscle aging. The Ingenuity Pathway Analysis pinpointed 17β-estradiol as a potential upstream regulator of the observed differences in the major downstream pathways including dysregulated cell death and glycolysis pathways. The results increase knowledge on the factors related to skeletal muscle signaling and aging. This is of importance, since the role of female sex hormones in the regulation of muscle cell signaling has been under appreciated and scarcely studied as compared to vast amount of data on male sex hormones and skeletal muscle. Our results clearly demonstrate the also female sex hormones and HRT should be considered as potential active players and an intervention targets to promote women’s muscular health.
Project description:Combined menopausal hormone therapy is associated with increased breast cancer risk in postmenopausal women. In our previous studies, progesterone receptor membrane component 1 (PGRMC1) was shown to play a role in progestins’ mode of action, resulting in enhanced proliferation of breast cancer cells. Here we describe a potential mechanism by which PGRMC1 contributes to breast cancer progression via interaction with prohibitins, inhibiting their function as transcription factor repressors, thereby facilitating estrogen receptor alpha (ERα) transcriptional activity and enhancing oncogenic signaling upon treatment with certain progestins, such as norethisterone and dydrogesterone.
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:Physical exercise has a positive effect on increasing or maintaining BMD in both pre-menopausal and postmenopausal women. The underlying mechanisms of physical exercise on the osteoblast (OB) in estrogen deficiency are not well understood. We used microarray to analyze the transcriptome of OB in ovariectomized mice, with or without physical exercise. intervention.
Project description:Global proteomic profiling of three mammary epithelial cell types in normal human breast tissue. Primary breast specimens were obtained from 10 women undergoing reduction mammoplasties. Clinical co-variates include age (28-67), hormone status (follicular, luteal, post-menopausal) and mammary epithelial cell type (basal, luminal progenitor, mature luminal).