Abstract
Purpose
To investigate the association of partial-AZFc deletions in Chilean men with primary spermatogenic failure and their testicular histopathological phenotypes, analyzing the contribution of DAZ dosage, CDY1 copies, and Y-chromosome haplogroups.
Subjects and methods
We studied 479 Chilean men: 334 infertile patients with histological examination (233 cases with spermatogenic defects and 101 normal spermatogenesis, obstructive controls, OC), and 145 normozoospermic controls (NC). AZFc subdeletions were detected by single-tagged sequences and single nucleotide variants analysis. DAZ-copy number was quantified by real-time qPCR. Y-chromosome haplogroups (Y-hg) were hierarchically genotyped through 16 biallelic-markers.
Results
The prevalence of AZFc-partial deletions was increased in cases (6%) compared with NC (1.4%) (P = 0.035). There was no difference between 143 Sertoli-cell only syndrome, 35 maturation arrest, or 35 mix atrophy patients and controls. However, gr/gr deletions were more frequent in 16 subjects with hypospermatogenesis compared with NC (P = 0.003) and OC (P = 0.013). Y-hg R was the most prevalent (~ 50%), but decreased among gr/gr deletions (21%, P = 0.03). The prevalence of Y-hg M increased in cases versus controls, both in total and non-deleted men (3.9 and 3.7% versus 0.4%, P = 0.009 and P = 0.016, respectively). Among gr/gr deletions, Y-hg H increased compared with non-deleted men (14.3% versus 0.4%, P = 0.0047).
Conclusion
Partial-AZFc deletions in a Chilean admixed population are associated with secretory azo/oligozoospermia and might have a role in the development of hypospermatogenesis. Low represented haplogroups, Y-hg M and Y-hg H, show an association with the occurrence of spermatogenic failure and gr/gr deletions respectively; however, additional studies are required.
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Acknowledgments
We are grateful to all the patients who participated in this study.
Funding
This work was supported by the National Fund for Scientific and Technological Development of Chile (FONDECYT), grants numbers 1030984 and 1120176, and by the University of Chile, Overhead #560228 to A.C.
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M.C.L. contributed in the design and supervising of qPCR and PCR-RFLP for DAZ analysis, performed interpretation of results, and revised the manuscript. V.O. performed DAZ quantification and collaborated in the recruitment of subjects. E.O. contributed with the CDY1 analysis and collaborated in protocols for the determination of the Y-chromosome haplogroups and DAZ quantification. M.F. participated in the recruitment and clinical evaluation of the patients, PCR analysis for detections of Yq-microdeletions and characterization of partial-AZFc deletions. M.E. recruited infertile men and performed the andrological assessments and testicular biopsies. A.P. performed the histological analysis of the testicular biopsies. S.F. contributed to the design and determination of the Y-chromosome haplogroups. P.P. contributed to the design and determination of the Y-chromosome haplogroups. M.O. contributed to the design and determination of the Y-chromosome haplogroups. M.M. contributed in the design, direction, and supervising of experimental protocols for determinations of the Y-chromosome haplogroups, critical analysis, and revision of the manuscript. A.C. wrote the paper, conceived the study, directed the experimental protocols, and analyzed and interpreted the results.
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The Institutional Review Boards of the University of Chile, School of Medicine, and Hospital Clínico San Borja Arriarán (Santiago, Chile) approved the study in accordance with the Helsinki Declaration, and all subjects gave their informed consent.
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María Cecilia Lardone and Victoria Ortega should be considered as joint first authors
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Lardone, M.C., Ortega, V., Ortiz, E. et al. Partial-AZFc deletions in Chilean men with primary spermatogenic impairment: gene dosage and Y-chromosome haplogroups. J Assist Reprod Genet 37, 3109–3119 (2020). https://doi.org/10.1007/s10815-020-01957-6
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DOI: https://doi.org/10.1007/s10815-020-01957-6