The Y chromosome-linked copy number variations and male fertility

J Endocrinol Invest. 2011 May;34(5):376-82. doi: 10.1007/BF03347463. Epub 2011 Mar 21.


Since the first definition of the AZoospermia Factor (AZF) regions, the Y chromosome has become an important target for studies aimed to identify genetic factors involved in male infertility. This chromosome is enriched with genes expressed exclusively or prevalently in the testis and their absence or reduction of their dosage is associated with spermatogenic impairment. Due to its peculiar structure, full of repeated homologous sequences, the Y chromosome is predisposed to structural rearrangements, especially deletions/ duplications. This review discusses what is currently known about clinically relevant Y chromosome structural variations in male fertility, mainly focusing on copy number variations (CNVs). These CNVs include classical AZF deletions, gr/gr deletion and TSPY1 CNV. AZF deletions are in a clear-cut causeeffect relationship with spermatogenic failure and they also have a prognostic value for testis biopsy. gr/gr deletion represents the unique example in andrology of a proven genetic risk factor, providing an eight-fold increased risk for oligozoospermia in the Italian population. Studies on TSPY1 CNV have opened new perspectives on the role of this gene in spermatogenic efficiency. Although studies on the Y chromosome have importantly contributed to the identification of new genetic causes and thus to the improvement of the diagnostic work-up for severe male factor infertility, there is still about 50% of infertile men in whom the etiology remains unknown. While searching for new genetic factors on other chromosomes, our work on the Y chromosome still needs to be completed, with special focus on the biological function of the Y genes.

Publication types

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

MeSH terms

  • Cell Cycle Proteins / genetics
  • Chromosomes, Human, Y / genetics*
  • DNA Copy Number Variations*
  • Gene Deletion
  • Genetic Loci
  • Genetic Testing
  • Humans
  • Infertility, Male / diagnosis
  • Infertility, Male / genetics*
  • Male
  • Oligospermia / genetics
  • Seminal Plasma Proteins / genetics


  • Cell Cycle Proteins
  • Seminal Plasma Proteins
  • TSPY1 protein, human