Spermatogenic failure and the Y chromosome

Hum Genet. 2017 May;136(5):637-655. doi: 10.1007/s00439-017-1793-8. Epub 2017 Apr 29.


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.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Deletion
  • Chromosomes, Human, Y / genetics*
  • DNA Copy Number Variations
  • Humans
  • Infertility, Male / genetics
  • Male
  • Oligospermia / genetics
  • Sequence Deletion
  • Spermatogenesis / genetics*