Identification of testis-specific male contraceptive targets: Insights from transcriptional profiling of the cycle of the rat seminiferous epithelium and purified testicular cells

Daniel S. Johnston, Scott A. Jelinsky, Yu Zhi, Joshua N. Finger, Gregory S. Kopf, William W. Wright

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

In an effort to identify novel targets for the development of nonhormonal male contraceptives, genome-wide transcriptional profiling of the rat testis was performed. Specifically, enzymatically purified spermatogonia plus early spermatocyctes, pachytene spermatocytes, round spermatids, and Sertoli cells was analyzed along with microdissected rat seminiferous tubules at stages I, II-III, IV-V, VI, VIIa,b, VIIc,d, VIII, IX- XI, XII, XIII-XIV of the cycle of the seminiferous epithelium using RAE 230_2.0 microarrays. The combined analysis of these studies identified 16,971 expressed probe sets on the array. How these expression data, combined with additional bioinformatic data analysis and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis, led to the identification of 58 genes that have 1000-fold higher expression transcriptionally in the testis when compared to over 20 other nonreproductive tissues is described. The products of these genes may play important roles in testicular and/or sperm function, and further investigation on their utility as nonhormonal contraceptive targets is warranted. Moreover, these microarray data have been used to expedite the identification of a mutation in RIKEN cDNA 2410004F06 gene as likely being responsible for spermatogenic failure in a line of infertile mice generated by N-ethyl-N-nitrosourea (ENU) mutagenesis. The microarray data and the qRT-PCR data described are available in the Mammalian Reproductive Genetics database (http://mrg.genetics.washington.edu/).

Original languageEnglish (US)
Title of host publicationTesticular Chromosome Structure and Gene Expression
PublisherBlackwell Publishing Inc.
Pages36-46
Number of pages11
ISBN (Print)9781573316934
DOIs
StatePublished - Dec 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1120
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Contraception
  • Microarray
  • Seminferous epithelium
  • Testis
  • Testis-specific

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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