2093 A ROLE FOR THE GLUCOSE TRANSPORTER GLUT3 IN MALE FERTILITY

Abstract

You have accessJournal of UrologyInfertility: Physiology, Pathophysiology, Basic Research1 Apr 20122093 A ROLE FOR THE GLUCOSE TRANSPORTER GLUT3 IN MALE FERTILITY Alexander W. Pastuszak, Carolina J. Jorgez, Larry I. Lipshultz, and Dolores J. Lamb Alexander W. PastuszakAlexander W. Pastuszak Houston, TX More articles by this author , Carolina J. JorgezCarolina J. Jorgez Houston, TX More articles by this author , Larry I. LipshultzLarry I. Lipshultz Houston, TX More articles by this author , and Dolores J. LambDolores J. Lamb Houston, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2260AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Approximately 15% of couples encounter fertility problems, with a 50% male factor contribution. In many of these men, a genetic cause is suspected. While numerous known genetic alterations cause male infertility, it is likely that many other genetic etiologies exist. Glucose transporters (GLUTs) may be involved in sperm motility, though their functional role in this process is unclear and no genetic studies exist supporting a role for GLUTs in fertility. Here, we present genomic data implicating the glucose transporter GLUT3 in male fertility. METHODS Blood-derived genomic DNA from 16 men with non-obstructive azoospermia (NOA) and normal Y-chromosome microdeletion and karyotype analyses, as well as 4 fertile male controls, was hybridized to microarrays and comparative genomic hybridization (aCGH) performed (3x720k Whole-Genome Tiling Array, Roche Nimblegen, Inc.) to assess for copy number variations (CNVs). Copy number gains and losses were identified after baseline correction using Nexus Copy Number software (BioDiscovery, Inc.) and candidate fertility genes selected based on 1) the frequency of CNVs in the gene, 2) the magnitude of the gain / loss, 3) evidence supporting a potential role in male fertility, and 4) available data on gene expression. Gene copy numbers were validated using Taqman qPCR, and Sanger DNA sequencing performed to assess for single nucleotide polymorphisms (SNPs) within genes of interest. Immunohistochemical staining of testis sections utilized commercially available antibodies and standard protocols. RESULTS Copy number gains were identified using aCGH in GLUT3 in 2 of 16 patients, and in no controls. These gains were confirmed in both patients using Taqman qPCR copy number assays. Subsequent Taqman assays of DNA from 43 infertile men yielded 5 more men with GLUT3 gains. Of note, the frequency of GLUT3 CNVs in the general population (which includes infertile as well as fertile individuals) is approximately 5%, whereas our observed gain frequency is 16%. Sequencing of GLUT3 yielded SNPs in exons 2 (2465 A>C, 36 K>T), 6 (6505 A>G, 258 L>L), and 10 (14680 C>T, 436 T>T), none of which were predicted to be damaging. Staining for GLUT3 in testis sections of a male with 3 copies of GLUT3 and hypospermatogenesis demonstrated cytoplasmic Leydig cell and spermatocyte staining. CONCLUSIONS Copy number gains in GLUT3 were identified in several infertile males. Future work in the form of functional assays analyzing the impact of GLUT3 expression on fertility-related cell signaling pathways, as well as the study of animal models, will further elucidate the role of GLUT3 in male fertility. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e844 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander W. Pastuszak Houston, TX More articles by this author Carolina J. Jorgez Houston, TX More articles by this author Larry I. Lipshultz Houston, TX More articles by this author Dolores J. Lamb Houston, TX More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...