TENR gene mutations in infertile males who display oligospermia or azoospermia. T.D. Brown, L.P. Chorich, L.C. Layman. Dept of Ob/Gyn, Section of Reproductive Endocrinology, Infertility, & Genetics, Developmental Neurobiology Program, Institute of Molecular Medicine & Genetics, Medical College of Georgia, Augusta, GA.
   The successful differentiation of male spermatids into mature spermatozoa is vital for normal fertility in the final stages of spermiogenesis. Tenr, an RNA binding protein, is exclusively expressed in the testis and appears to be involved in spermiogenesis. Disruption of this gene is predicted to interfere with male fertility. Homozygous male Tenr knockout mice exhibited infertility and no litters due to a 6-fold lower number of sperm in the epididymis, a 3-fold reduction in motility, and a 4.5-fold increase in abnormal sperm morphology. The purpose of the present study was to determine if TENR mutations occur in infertile human males who display oligospermia or azoospermia and to demonstrate TENR expression in human sperm. The TENR protein coding region (exons 3-13) and splice junctions from the genomic DNA of 66 infertile males (13 with azoospermia and 53 with oligospermia) and controls were subjected to PCR, agarose gel electrophoresis, and DNA sequencing. A silent mutation (Tyr338Tyr) c.270 C>T in exon 4 was identified; it was homozygous mutant in 2/64, heterozygous in 12/64, and homozygous wild type in 50 /64. To date, it has not been identified in controls. In addition, another potential mutation was identified in an intron (IVS12+20A>G); it was heterozygous mutant in 2/43 patients analyzed. We are currently determining if these mutations affect splicing of mRNA. Human TENR expression was demonstrated by RT-PCR in a control male with the presence of a predicted 2kb fragment using TENR-specific primers. The TENR gene represents a reasonable candidate gene for mutations in infertile males with abnormal semen analyses. However it appears that TENR gene mutations may not be a common cause of infertility in oligospermic or azoospermic males.