Identification of ten novel genes involved in human spermatogenesis by microarray analysis of testicular tissue

Objective To identify novel genes that are down-regulated in the testicular tissue of infertile men. Design Prospective study. Setting University-based reproductive clinics and genetics laboratory. Patients Nine patients with normal spermatogenesis, and 15 patients with maturation arrest (MA) or Sertoli cell-only syndrome (SCOS). Intervention Testicular samples of patients with the same histology were pooled for complementary DNA (cDNA) microarray analysis. Main Outcome Measure Novel, down-regulated genes. Results In total, 300 genes were significantly down-regulated in SCOS or MA samples, and 10 novel sterility-related genes were identified. Of the 10 novel genes, 6 genes (Hs.126780, Hs.553658, Hs.274135, Hs.268122, Hs.531701, and Hs.171130) encode proteins with predictable functional domains, and all these functional domains are believed to correlate with spermatogenesis and/or spermiogenesis. Conversely, the other 4 genes (Hs.351582, Hs.407480, Hs.552781, and Hs.355570) do not encompass known functional domains. Two genes (Hs.407480 and Hs.552781) lack mouse orthologues. Most novel genes showed a testis-specific expression pattern in both mice and humans. Reverse transcription-polymerase chain reaction (RT-PCR) showed three distinct types of developmental stage-dependent expressions of message ribonucleic acid (mRNA) for these novel genes in murine testes. Conclusion These 10 novel genes provide targets to elucidate novel pathways involved in human spermatogenesis.