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Spermatogenic failure and the Y chromosome

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Abstract

The Y chromosome harbors a number of genes essential for testis development and function. Its highly repetitive structure predisposes this chromosome to deletion/duplication events and is responsible for Y-linked copy-number variations (CNVs) with clinical relevance. The AZF deletions remove genes with predicted spermatogenic function en block and are the most frequent known molecular causes of impaired spermatogenesis (5–10% of azoospermic and 2–5% of severe oligozoospermic men). Testing for this deletion has both diagnostic and prognostic value for testicular sperm retrieval in azoospermic men. The most dynamic region on the Yq is the AZFc region, presenting numerous NAHR hotspots leading to partial losses or gains of the AZFc genes. The gr/gr deletion (a partial AZFc deletion) negatively affects spermatogenic efficiency and it is a validated, population-dependent risk factor for oligozoospermia. In certain populations, the Y background may play a role in the phenotypic expression of partial AZFc rearrangements and similarly it may affect the predisposition to specific deletions/duplication events. Also, the Yp contains a gene array, TSPY1, with potential effect on germ cell proliferation. Despite intensive investigations during the last 20 years on the role of this sex chromosome in spermatogenesis, a number of clinical and basic questions remain to be answered. This review is aimed at providing an overview of the role of Y chromosome-linked genes, CNVs, and Y background in spermatogenesis.

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Acknowledgements

The authors thank Prof. G. Forti for his continuous support of research on the Y chromosome; we are also grateful to the ex and current members of the Molecular Genetic laboratory (responsible C Krausz), C. Giachini, C. Chianese, D. Lo Giacco, E. Guarducci, S. Degl’Innocenti, I. Laface, S. Vinci, M. Fino, and A. Riera-Escamilla for their contribution to the original data presented in this review. Funding from the Istituto Toscano Tumori (ITT) grant 2013-2016 to CK is acknowledged.

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  1. Department of Experimental, Clinical and Biomedical Sciences Mario Serio, Sexual Medicine and Andrology Unit, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy

    C. Krausz & E. Casamonti

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  1. C. Krausz
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  2. E. Casamonti
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Correspondence to C. Krausz.

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Krausz, C., Casamonti, E. Spermatogenic failure and the Y chromosome. Hum Genet 136, 637–655 (2017). https://doi.org/10.1007/s00439-017-1793-8

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  • DOI: https://doi.org/10.1007/s00439-017-1793-8

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