Study of azoospermia factor-a deletion caused by homologous recombination between the human endogenous retroviral elements and population-specific alleles in Japanese infertile males

ObjectiveTo evaluate the relationship between the status of homologous recombination and population-specific alleles in infertile Japanese males with azoospermia factor (AZF)-a deletions and to characterize the clinical features of these patients.DesignRetrospective deletion study in infertile Japanese men.SettingUniversity hospital and reproductive clinic.Patient(s)A total of 931 consecutive patients visiting a male-infertility clinic were genetically evaluated.Intervention(s)Patients were analyzed for Y-chromosomal microdeletions and the breakpoints of intrachromosomal homologous recombination of human endogenous retrovirus (HERV) 15qy; in addition, Y-haplogroup typing on the basis of polymerase chain reaction also was performed. Endogenous retroviruses contribute to the evolution of the host genome and can be associated with disease.Main Outcome Measure(s)Presence or absence of appropriately sized polymerase chain reaction products.Result(s)Four cases of AZFa deletions were found. All patients with AZFa deletions had an azoospermia and breakpoints in the ID2 region of HERV15qy. Three of the four cases were derived from Y-haplogroup D2b. Testicular sperm extraction procedures were performed in three of these four patients, and elongated spermatids were recovered in two. However, no pregnancies were successfully achieved.Conclusion(s)Y-haplotype D2b, specific for some Japanese clade, may be associated with HERV breakpoints that lead to intrachromosomal homologous recombination. From the clinical point of view, the testicular sperm extraction procedure is not applicable to males with complete AZFa deletions.