Mouse anti-Human EIF1AY monoclonal antibody, clone 2C5

Deletions of the Y chromosome are a significant cause of spermatogenic failure. Three major deletion intervals have been defined and termed AZFa, AZFb and AZFc. Here, we report an unusual case of a proximal AZFb deletion that includes the Y chromosome palindromic sequence P4 and a novel heat shock factor (HSFY). This deletion neither include the genes EIF1AY, RPS4Y2 nor copies of the RBMY1 genes. The individual presented with idiopathic azoospermia. We propose that deletions of the testis-specific HSFY gene family may be a cause of unexplained cases of idiopathic male infertility. This deletion would not have been detected using current protocols for Y chromosome microdeletion screens, therefore we recommend that current screening protocols be extended to include this region and other palindrome sequences that contain genes expressed specifically in the testis.

BACKGROUND: The Y-chromosome AZF regions include genes whose functions and specific roles in spermatogenesis have not been fully clarified. This study investigated the expression of several AZF (USP9Y, DDX3Y/DDX3Yt1, EIF1AY and PRY) and USP9X transcripts in testicular biopsies of 89 azoospermic men who had been classified by histology and cytology assessments. METHODS: Expression was analysed by RT-PCR, and some biopsies were evaluated by multiplex RT-PCR. Quantitative PCR was performed in some biopsies to determine the ratio of the testis-specific transcript DDX3Yt1 to the total DDX3Y transcription. RESULTS: The expression of USP9Y, USP9X and DDX3Y was found in all the specimens tested, whereas DDX3Yt1 expression was diminished or undetectable in several biopsies with impaired spermatogenesis. EIF1AY was detected in all except two of the specimens. Noteworthy, PRY expression was detected mainly in biopsies with germ cells, and this association was significant (P < 0.001). An identical expression profile was obtained by either single or multiplex RT-PCR. CONCLUSIONS: These findings suggest that PRY is usually expressed in germ cells, whereas the other transcripts are also expressed in testicular somatic cells. The absence of EIF1AY expression might sporadically contribute to azoospermia. The decreased ratio of DDX3Yt1/DDX3Y transcript in impaired spermatogenesis suggests that the DDX3Yt1 transcript is under-expressed in impaired spermatogenesis. The findings contribute to the search and selection of the most valuable gene markers potentially useful as additional tools for predicting complete spermatogenesis by multiplex expression analysis.