title: A significant effect of the TSPY1 copy number on spermatogenesis efficiency and the phenotypic expression of the gr/gr deletion.
abstract: AZFc deletions cause a significant phenotypic heterogeneity with respect to spermatogenesis; however, the reason for this is poorly understood. Recently, testis-specific protein Y-encoded 1 (TSPY1) copy number variation (CNV) was determined to be a potential genetic modifier of spermatogenesis. We performed a large-scale cohort study to investigate the effect of TSPY1 CNV on spermatogenesis and to elucidate the possible contribution of TSPY1 genetic variation to the phenotypic expression of AZFc deletions. Haplogrouping of the Y-chromosome and quantification of the TSPY1 copy number were performed in 2272 Han Chinese males with different spermatogenic statuses (704 males with the b2/b4 or gr/gr deletion and 1568 non-AZFc-deleted males). Our data revealed that the TSPY1 copy number distributions were significantly different among non-AZFc-deleted males with different spermatogenic phenotypes. Lower sperm production and an elevated risk of spermatogenic failure were observed in males with fewer than 21 TSPY1 copies and in those with more than 55 copies relative to men with 21-35 copies. Similar results were observed in males with the gr/gr deletion. These findings indicate that TSPY1 CNV affects an individual's susceptibility to spermatogenic failure by modulating the efficiency of spermatogenesis and strongly suggest that there is a significant quantity effect of the TSPY1 copy number on the phenotypic expression of the gr/gr deletion. To our knowledge, this CNV is the first independent genetic factor that has been clearly observed to influence the spermatogenic status of gr/gr deletion carriers. A combined genetic analysis of the TSPY1 copy number and the gr/gr deletion could inform the clinical counselling of infertile couples.
authors: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China.
authors: Ying
authors: Y
authors: Shen
authors: Yuanlong
authors: Y
authors: Yan
authors: Yunqiang
authors: Y
authors: Liu
authors: Sizhong
authors: S
authors: Zhang
authors: Dong
authors: D
authors: Yang
authors: Peng
authors: P
authors: Zhang
authors: Lei
authors: L
authors: Li
authors: Yan
authors: Y
authors: Wang
authors: Yongxin
authors: Y
authors: Ma
authors: Dachang
authors: D
authors: Tao
authors: Yuan
authors: Y
authors: Yang
mesh_terms: D000328:Adult; D044466:Asian People; D053713:Azoospermia / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002681:China; D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics*; D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009845:Oligospermia / Q000235:genetics; D010641:Phenotype; D013091:Spermatogenesis / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C497749:TSPY1 protein, human