MP76-18 MALE INFERTILITY AND SINGLE NUCLEOTIDE POLYMORPHISMS OF THE NOVEL SEX-LINKED TESTIS-SPECIFIC RETROTRANSPOSED PGAM4 GENE

Abstract

You have accessJournal of UrologyInfertility: Basic Research, Physiology, Pathophysiology1 Apr 2015MP76-18 MALE INFERTILITY AND SINGLE NUCLEOTIDE POLYMORPHISMS OF THE NOVEL SEX-LINKED TESTIS-SPECIFIC RETROTRANSPOSED PGAM4 GENE Yasushi Miyagawa, Tetsuji Soda, Kentaro Takezawa, Shinichiro Fukuhara, Hiroshi Kiuchi, Hidenobu Okuda, Hiromitsu Tanaka, and Norio Nonomura Yasushi MiyagawaYasushi Miyagawa More articles by this author , Tetsuji SodaTetsuji Soda More articles by this author , Kentaro TakezawaKentaro Takezawa More articles by this author , Shinichiro FukuharaShinichiro Fukuhara More articles by this author , Hiroshi KiuchiHiroshi Kiuchi More articles by this author , Hidenobu OkudaHidenobu Okuda More articles by this author , Hiromitsu TanakaHiromitsu Tanaka More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2934AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In man, infertility is demonstrated to be associated with various genetic factors. However, all of them are neither conclusive as the causative gene nor explain all idiopathic male infertility. Multiple studies, primarily through the use of transgenic animals, have contributed to a list of candidate genes that may affect male infertility in humans. We examined single nucleotide polymorphisms (SNPs) as a cause of male infertility in an analysis of spermatogenesis-specific genes. METHODS Since the genomic DNA is known to be intronless, we checked the existence of single nucleotide changes in the genome of human PGAM4 in male sterile patients and compared with that of proven fertile normal volunteers by using a polymerase chain reaction technique. RT-PCR and western blot analyses were also performed to check the expression of PGAM4 in testis and sperm. Finally, We investigated whether there might be any PGAM4 genetic variants affecting male fertility by performing a case-control study of fertile and infertile men. RESULTS Using RT-PCR and western blot analyses, we identified that PGAM4 is a functional retrogene that is expressed predominantly in the testes and is associated with male infertility. PGAM4 is expressed in post-meiotic stages, including spermatids and spermatozoa in the testes, and the principal piece of the flagellum and acrosome in ejaculated spermatozoa. A case-control study revealed that 4.5% of infertile patients carry the G75C polymorphism, which causes an amino acid substitution in the encoded protein. Prevalence of PGAM4 SNPs in infertile and proven-fertile human populations were indicated in Table. Furthermore, an assay for enzymatic activity demonstrated that this polymorphism decreases the enzyme's activity both in vitro and in vivo. CONCLUSIONS These results suggest that PGAM4, an X-linked retrogene, is a fundamental gene in human male reproduction and may escape meiotic sex chromosome inactivation. These findings provide fresh insight into elucidating the mechanisms of male infertility. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e990-e991 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasushi Miyagawa More articles by this author Tetsuji Soda More articles by this author Kentaro Takezawa More articles by this author Shinichiro Fukuhara More articles by this author Hiroshi Kiuchi More articles by this author Hidenobu Okuda More articles by this author Hiromitsu Tanaka More articles by this author Norio Nonomura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...