Molecular analysis of the vaginal response to estrogens in the ovariectomized rat and postmenopausal woman

<p>Abstract</p> <p>Background</p> <p>Vaginal atrophy (VA) is the thinning of the vaginal epithelial lining, typically the result of lowered estrogen levels during menopause. Some of the consequences of VA include increased susceptibility to bacterial infection, pain during sexual intercourse, and vaginal burning or itching. Although estrogen treatment is highly effective, alternative therapies are also desired for women who are not candidates for post-menopausal hormone therapy (HT). The ovariectomized (OVX) rat is widely accepted as an appropriate animal model for many estrogen-dependent responses in humans; however, since reproductive biology can vary significantly between mammalian systems, this study examined how well the OVX rat recapitulates human biology.</p> <p>Methods</p> <p>We analyzed 19 vaginal biopsies from human subjects pre and post 3-month 17β-estradiol treated by expression profiling. Data were compared to transcriptional profiling generated from vaginal samples obtained from ovariectomized rats treated with 17β-estradiol for 6 hrs, 3 days or 5 days. The level of differential expression between pre- vs. post- estrogen treatment was calculated for each of the human and OVX rat datasets. Probe sets corresponding to orthologous rat and human genes were mapped to each other using NCBI Homologene.</p> <p>Results</p> <p>A positive correlation was observed between the rat and human responses to estrogen. Genes belonging to several biological pathways and GO categories were similarly differentially expressed in rat and human. A large number of the coordinately regulated biological processes are already known to be involved in human VA, such as inflammation, epithelial development, and EGF pathway activation.</p> <p>Conclusion</p> <p>At the transcriptional level, there is evidence of significant overlap of the effects of estrogen treatment between the OVX rat and human VA samples.</p

A scatterplot of the average t-statistic of estradiol treated vaginal tissue compared to untreated vaginal tissue for each of the human gene sets compared to the average t-statistic for each of the rat gene sets

Each point represents a distinct gene set. A positive correlation is seen suggesting many of the gene sets are coordinately regulated. Gene sets in the upper right and lower left corners represent gene sets that are significantly regulated in both rat and human.<p><b>Copyright information:</b></p><p>Taken from "Molecular analysis of the vaginal response to estrogens in the ovariectomized rat and postmenopausal woman"</p><p>BMC Medical Genomics 2008;1():27-27.</p><p>Published online 25 Jun 2008</p><p>PMCID:PMC2453134.</p><p></p

Messenger RNA levels for (A) , (B) , (C) , (D) , (E) and (F) are shown for each individual treatment

<p><b>Copyright information:</b></p><p>Taken from "Molecular analysis of the vaginal response to estrogens in the ovariectomized rat and postmenopausal woman"</p><p>http://www.biomedcentral.com/1755-8794/1/27</p><p>BMC Medical Genomics 2008;1():27-27.</p><p>Published online 25 Jun 2008</p><p>PMCID:PMC2453134.</p><p></p

Plotted is the normalized t-statistics for differential expression on the x-axis plotted against the fraction of the gene set that has that x-value or lower on the y-axis

Gene sets that are shifted away from the plot of the entire data set are considered to be significant. (A) Genes involved in TGFβ signaling are down regulated in both species. (B) Genes involved in cholesterol biosynthesis are up regulated in both species.<p><b>Copyright information:</b></p><p>Taken from "Molecular analysis of the vaginal response to estrogens in the ovariectomized rat and postmenopausal woman"</p><p>http://www.biomedcentral.com/1755-8794/1/27</p><p>BMC Medical Genomics 2008;1():27-27.</p><p>Published online 25 Jun 2008</p><p>PMCID:PMC2453134.</p><p></p

Abstract 3884: Stroke Subtypes in Hispanic Patients in the NINDS Stroke Genetics Network (SiGN): A Comparison of Two Classification Systems

Objectives: Identification of gene variants of stroke subtypes is important for the development of tailored ischemic stroke therapies among various ethnic groups. Valid and reliable determination of ischemic stroke subtype is essential for achieving this goal and to standardize a classification scheme across multi-center studies and different populations. Causative Classification System for Ischemic Stroke (CCS) is a novel computerized subclassification tool developed to improve reliability and accuracy of classifying stroke types. The CCS algorithm relies on both phenotypic and causative stroke variables. A Hispanic subset of the SiGN, an important and distinct target population with greater risk of certain stroke subtypes, was evaluated with Trial of Org 10172 in Acute Stroke Treatment (TOAST) and CCS and the agreement between the two classification systems was analyzed. Methods: Over 6000 subjects at 15 sites across US and Europe were enrolled, with TOAST and CCS locally adjudicated. Blood collection and central data quality control (10% central readjudication) were performed on all participants. A subset of Hispanics was analyzed for the purpose of this study and the agreement between the TOAST and CCS were assessed by kappa statistic. Findings: Hispanics (n=595, 10.9%) compared to non-Hispanics (n=5457) were more likely to be younger (63.7 vs. 64.0), male (55% vs. 46%) and have fewer of the traditional stroke risk factors HTN (54% vs. 64%), Afib (11% vs. 14%), DM(23% vs. 25%), CAD(16% vs. 20%) and smoking(19% vs. 22%). While the TOAST showed no differences between stroke subtypes for Hispanic vs. non-Hispanics, in CCS, Hispanics were classified with more of large vessel (22% vs. 20%), cardioembolic (37% vs. 30%) and small vessel strokes (13% vs. 9%) and fewer with undetermined etiology (28% vs. 40%) as compared to non-Hispanics. TOAST and CCS offered moderate correlation across all stroke types in Hispanics: kappa of 0.66 for large artery atherosclerosis, 0.58 for cardioembolic, and 0.58 for small artery occlusion. Conclusion: CCS offers a more sensitive and accurate system for subphenotyping of strokes in Hispanics who tended to have relatively fewer risk factors and unclassified strokes. Further studies correlating the two classification systems and their relation to genotyping data are warranted