title: Common AZFc structure may possess the optimal spermatogenesis efficiency relative to the rearranged structures mediated by non-allele homologous recombination.
abstract: The azoopsermia factor c (AZFc) region of human Y-chromosome is an essential genomic segment for spermatogenesis with frequent non-allele homologous recombination (NAHR). Recent case-control studies on the association of the NAHR-based AZFc structural mutations with spermatogenic failure produced inconsistent results. To more precisely evaluate their spermatogenesis effects, we investigated the correlation between the subdivided AZFc mutations and sperm production in 3,439 Han Chinese males. Our results showed that both partial AZFc deletion-only and primary duplication mutation presented a significant risk for decreased sperm production. Restoration of the reduced dosage of the AZFc content to the normal level had a milder effect, whereas an overdose of the AZFc content arising from multiple duplications of a partial AZFc-deleted structure produced a more serious consequence compared to the partial deletion-only mutation. Additionally, the AZFc-mutated structures with excessive NAHR-substrate showed a notably negative effect on spermatogenesis. These results suggest that the recurrent NAHR-based AZFc mutations may be associated with decreased spermatogenesis efficiency in present population. More significantly, our finding implies that the overdose of AZFc NAHR-substrate may produce an additional risk for the massive AZFbc deletions during the multi-stage division process of germ cells and thus impair the global spermatogenesis efficiency in the carriers.
authors.affiliation: Department of Urology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Yong-yi
authors.initials: YY
authors.lastname: Ma
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Yun-qiang
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Reproductive Medicine Centre, West China Second Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Reproductive Medicine Institute, Chengdu Women's &Children's Central Hospital, Chengdu 610031, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Wen-ling
authors.initials: WL
authors.lastname: Tu
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Urology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D041322:Chromosomes, Human, Y / Q000737:chemistry / Q000235:genetics*; D000075364:Deleted in Azoospermia 1 Protein; D017353:Gene Deletion; D018628:Gene Dosage; D006239:Haplotypes; D059765:Homologous Recombination; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000473:pathology; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016017:Odds Ratio; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D013091:Spermatogenesis; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*
chemical_list: C118459:CDY1 protein, human; C095668:DAZ1 protein, human; D000075364:Deleted in Azoospermia 1 Protein; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins