Background: The relationship between male infertility and gr/gr deletions that remove multiple genes of the Y chromosome varies among countries and populations. The aim of this study was to investigate the association between gr/gr deletions and spermatogenic phenotype in fertile and infertile Japanese men.
Methods: The subjects were screened by sequence-tagged site (STS) analysis to detect gr/gr deletions, and haplogroups were assigned using eight highly informative markers. In total, 395 infertile men and 377 fertile men (controls) participated in our study. Of the 772 subjects, 260 individuals carried confirmed gr/gr deletions and were used in further analysis of deletion subtype and gene copy number, specifically loss and gain of CDY1 and DAZ copies. These 260 subjects were divided into a control group (n = 131) all with normozoospermia, and an infertile group (n = 129) with 89 infertile subjects exhibiting azoospermia (absence of sperm) and 40 exhibiting oligozoospermia (reduced sperm concentration).
Results: There were gr/gr deletions in 33.7% (260/772) of all subjects and the deletions were widespread in haplogroup D (86.2%). There were no significant differences in the frequency of gr/gr deletions between the infertile and control groups. The gr/gr deletion subtypes were not distributed randomly among haplogroups; the CDY1a+ DAZ1/2 genes were deleted in 96.9% (217/224) of haplogroup D individuals, whereas the O lineage had a variety of gr/gr deletion types. The loss of CDY1a+ DAZ1/2 was not associated with spermatogenic impairment in haplogroup D (P = 0.33).
Conclusions: Taken together, gr/gr deletions in haplogroup D occur constitutively, are associated with the loss of CDY1a + DAZ1/2 and are phenotypically neutral. Further studies are needed to establish whether Y-linked compensatory factors outside the AZFc region can counteract the pathogenic effect of a gr/gr deletion in the D lineage.