Consequences of Y chromosome microdeletions beyond male infertility

J Assist Reprod Genet. 2019 Jul;36(7):1329-1337. doi: 10.1007/s10815-019-01492-z. Epub 2019 Jun 18.


Purpose: The human Y chromosome plays a central role in sex determination and spermatogenesis. The azoospermia factor (AZF) loci on the Y chromosome contain genes that were thought to be testis specific with their deletions leading to spermatogenic failure. However, beyond the testis, the AZF genes (mainly those in AZFa and AZFb loci) are widely expressed in multiple tissues. Further, these genes are predicted to play roles in processes such as gene regulation and protein synthesis. These observations suggest that the AZF genes may have functions beyond regulation of fertility.

Results: Three major areas have emerged where alternations in AZF genes have effects beyond infertility. (1) Poor-quality embryos are generated in assisted reproduction when sperm from men harboring Y chromosome microdeletions are used, (2) a higher preponderance of neuropsychiatry disorders is observed in men with deletions in AZF genes, and (3) copy number variations and altered expression of AZF genes are found in several cancers.

Conclusion: While our data is preliminary and observational in nature, systematic studies are required to address how genetic alterations in the Y chromosome can affect the health of men beyond infertility. This information will provide a different perspective in the area of androgenetics and have implications in devising strategies for maintaining the overall well-being of infertile males.

Keywords: AZF; Brain; Cancer; Embryo; Extra-gonadal; Gonads; Infertility; Microdeletions; Testis; Y chromosome.

Publication types

  • Review

MeSH terms

  • Azoospermia / genetics*
  • Azoospermia / pathology
  • Chromosomes, Human, Y / genetics*
  • Gene Deletion*
  • Humans
  • Infertility, Male / genetics*
  • Infertility, Male / pathology
  • Male
  • Sex Determination Processes / genetics
  • Spermatogenesis / genetics
  • Spermatozoa / pathology