MP52-18 ROLE OF FIBROBLAST GROWTH FACTOR RECEPTORS IN LEYDIG CELL DEVELOPMENT

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research I1 Apr 2015MP52-18 ROLE OF FIBROBLAST GROWTH FACTOR RECEPTORS IN LEYDIG CELL DEVELOPMENT Andres Correa, Kenneth Walker, Daniel Bushnel, Caitlin Schaefer, Julia Schaffer, and Carlton Bates Andres CorreaAndres Correa More articles by this author , Kenneth WalkerKenneth Walker More articles by this author , Daniel BushnelDaniel Bushnel More articles by this author , Caitlin SchaeferCaitlin Schaefer More articles by this author , Julia SchafferJulia Schaffer More articles by this author , and Carlton BatesCarlton Bates More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1735AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The adult Leydig cell undergoes several stages of maturation during development which is closely regulated by luteinizing hormone (LH), thyroid hormone (TH) and androgens. Several studies have shown increased androgen production by Leydig cells when exposed to fibroblast growth factors (Fgfs). The role of Fgf signaling in Leydig cell development and function remains unknown. Our aims are to investigate 1) Leydig cell development and maturation using a lineage tracing marker 2) the effect fibroblast growth factor receptor 1 and 2 deletion on adult Leydig cell development and function METHODS Tbx18cre transgenic mice were bred to either a CAG/red fluorescent protein (RFP) reporter (for lineage tracing) or to Fgfr1 and Fgfr2 floxed mice (for conditional knockouts of the receptors). Immunohistochemisty assays were performed to assess the expression pattern of the Tbx18creCAG line in the testis. Sox9 and 3-âHSD were used as markers of Sertoli cells and Leydig cells respectively. Leydig cell development in the Fgfr knock-out model was determined by gene expression using Real Time PCR at day 1, 30, 45 and 60 post birth. Leydig cell maturity was assessed with the following gene library: fetal Leydig cell (Patched and Thsb2), immature (5-á-reductase) and mature (Cyp17a1, Ptgds, Sult1e1, and Hsd17b3) RESULTS Immunohistochemical analysis of the Tbx18creCAG mice revealed expression throughout testicular interstitial cells of both fetal and adult testis. Immunolabeling with 3-âHSD and Sox9 revealed co-labeling of the RFP and 3-âHSD, but not with Sox9, indicating that Tbx18cre gene expression was only in the Leydig cell. Tbx18creFgfr1/2 knock-out mice showed under-developed Wolffian duct-derived structures in post-pubertal mice compared to controls. Fetal Leydig cell gene expression markers between controls and the Fgfr1/2 knockouts were comparable from birth to maturity. Adult mutant mouse testicles did have increased expression of 5-á-reductase and decrease expression of Cyp17a1, Ptgds, and Sult1e1 consistent with lack of leydig cell maturation. CONCLUSIONS Tbx18cre mice express cre only in Leydig cells, starting in embryos, making it an ideal to lineage trace or manipulate gene expression in Leydig cells. Tbx18creFgfr1/2 knockout mice had increased expression of immature Leydig cell gene markers compared to controls, consistent with Leydig cell arresting in an immature state. Thus, Fgfr1 and 2 signaling appears to be critical for Leydig cell maturation from an immature to a mature state. Impaired Fgf signaling in the Leydig cell may be responsible for some forms idiopathic hypogonadism. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193 Issue 4S April 2015 Page: e634 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.Metrics Author Information Andres Correa More articles by this author Kenneth Walker More articles by this author Daniel Bushnel More articles by this author Caitlin Schaefer More articles by this author Julia Schaffer More articles by this author Carlton Bates More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...