Impaired Spermatogenesis and gr/gr Deletions Related to Y Chromosome Haplogroups in Korean Men

Abstract

Microdeletion of the Azoospermia Factor (AZF) regions in Y chromosome is a well-known genetic cause of male infertility resulting from spermatogenetic impairment. However, the partial deletions of AZFc region related to spermatogenetic impairment are controversial. In this study, we characterized partial deletion of AZFc region in Korean patients with spermatogenetic impairment and assessed whether the DAZ and CDY1 contributes to the phenotype in patients with gr/gr deletions. Total of 377 patients with azoo-/oligozoospermia and 217controls were analyzed using multiplex polymerase chain reaction (PCR), analysis of DAZ-CDY1 sequence family variants (SFVs), and quantitative fluorescent (QF)-PCR. Of the 377 men with impaired spermatogenesis, 59 cases (15.6%) had partial AZFc deletions, including 32 gr/gr (8.5%), 22 b2/b3 (5.8%), four b1/b3 (1.1%) and one b3/b4 (0.3%) deletion. In comparison, 14 of 217 normozoospermic controls (6.5%) had partial AZFc deletions, including five gr/gr (2.3%) and nine b2/b3 (4.1%) deletions. The frequency of gr/gr deletions was significantly higher in the azoo-/oligozoospermic group than in the normozoospermic control group (p = 0.003; OR = 3.933; 95% CI = 1.509–10.250). Concerning Y haplogroup, we observed no significant differences in the frequency of gr/gr deletions between the case and the control groups in the YAP+ lineages, while gr/gr deletion were significantly higher in azoo-/oligozoospermia than normozoospermia in the YAP− lineage (p = 0.004; OR = 6.341; 95% CI = 1.472–27.312). Our data suggested that gr/gr deletion is associated with impaired spermatogenesis in Koreans with YAP− lineage, regardless of the gr/gr subtypes.

Y-chromosome microdeletion and male infertility: a systematic review

“…Of the 32 selected studies 14 are from descriptive [1, 2, 4, 13, 24, 27-29, 31, 32, 34-37], 08 are cross-sectional [3,5,17,18,21,25,26,33], 05 are experimental [7,12,19,20,38], 03 are case reports [22,30,39] and 02 are case-control studies [10,23]. Studies have good methodological accuracy.…”

“…Studies have good methodological accuracy. The sample universe is quite heterogeneous, given the very design of the studies (22 case reports with 02 individuals up to 33 cross-sectional studies with 4, 441 individuals), age differences between individuals in the samples ranging from 17 years [10] to 66 years [21], as well as the origin of the patients who were: India [2,23,25,35], Brazil [3,31,34,36], China [4,10,17,18], Iran [1,7,19,21] Turkey [5,26,27] [20], Denmark [37], USA [22], england [38], Mexico [30], Serbia [28] and Venezuela [32]. Because of this situation, the data becomes divergent and the comparative analysis becomes troublesome.…”

“…al. [18] showed 8.5% Korean men had deletions in the segment gr/gr (P <0.003), 5.8% had deletions of the region b2/b3, 1.1% had deletions in the region b1/b3, 0.3% had deletions in the region B3/B4, totaling 15.6% subjects (P<0.001). The authors also indicate that partial deletions of AZFc region were more often found in men with insufficient spermatogenesis when compared with the control group [18].…”

“…Its etiopathogenesis is not well understood, however, it's known the importance of the role of microdeletion of subregions of the Ychromosome in the casuistry. The literature indicates that deletion of AZF, especially AZFc [12,19,32], is related to azoospermia [1,5,10,18,21,26,31,35], oligozoospermia [10,18,21,31,36] , infertility [4,24] or even normal fertility [7]. The absence of other loci is also underlined by the evidence: AZFa, AZFb, AZFd [10,20,21,23,25,29] and although the prevalence rates are not equidistant.…”

Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

“…It has been observed that the Europeans and the Han Chinese have a strong association of gr/gr deletions with male infertility [11,22,27]; the American and African men with gr/gr deletions do not seem to be susceptible to azoospermia or oligozoospermia [20,21,[28][29][30]. In the Asian population, the gr/gr deletions are not associated with male infertility in the Malaysian and Japanese men; a significant association has been observed in the Korean and Chinese men [20,21,27,[31][32][33]. In the context of Indian population, the association of AZFc subdeletions and male infertility is unclear.…”