A Novel Y Chromosome Microdeletion With the Loss of an Endogenous Retrovirus Related, Testis Specific Transcript in AZFb Region

Purpose: We identified the endogenous retroviruses associated with TTYs (testis specific transcripts linked to the Y) in the AZFb region. We evaluated the relationship between endogenous retroviruses, and TTY expression patterns and function in spermatogenesis. Materials and Methods: We identified family members of TTYs in the AZFb region using computational screening. After investigating the relationship between the endogenous retrovirus genome and TTY expression patterns we screened genomic polymerase chain reaction products from TTY13 amplified from 790 Japanese men, including 275 with azoospermia, 285 with oligozoospermia and 230 who were fertile. Results: Computational screening revealed that 3 members of the TTY family, TTY9, 10 and 13, were regulated by endogenous retroviruses in the AZFb region. Homologous recombination between long terminal repeat of the TTY13 associated human endogenous retrovirus-K14C resulted in TTY13 deletion events. These deletions were more common in patients with azoospermia and oligozoospermia than in fertile males. Specifically 15.63% of the azoospermia group, 10.88% of the oligozoospermia group and 0% of fertile controls had only the deletion variant, indicating an association between the homologous recombination rate and the severity of spermatogenesis failure that was statistically significant (p < 0.05). Conclusions: Because of the finding of what are to our knowledge novel microdeletions due to endogenous retrovirus in the AZFb region, our study raises the possibility that specific variations in genomic structure may contribute to some forms of human idiopathic male infertility.