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Consequences of Y chromosome microdeletions beyond male infertility

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Abstract

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.

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Acknowledgments

DM lab is funded by grants from Indian Council of Medical Research (ICMR), Government of India. SC is thankful to ICMR for the postdoctoral fellowship. The manuscript bears the NIRRH ID: IR/702/11-2018.

This study makes use of data generated by the DECIPHER community. A full list of centers who contributed to the generation of the data is available from http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk. Funding for the project was provided by The Wellcome Trust.

Tissue expression of the Y chromosome genes was retrieved from data sets in the Human Protein Atlas. Tissue distribution map of the Y chromosome genes was created using Morpheus, https://software.broadinstitute.org/morpheus.

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  1. Department of Molecular and Cellular Biology, ICMR-National Institute for Research in Reproductive Health, JM Street, Parel, Mumbai, Maharashtra, 400012, India

    Stacy Colaco & Deepak Modi

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  1. Stacy Colaco
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  2. Deepak Modi
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Correspondence to Stacy Colaco or Deepak Modi.

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Colaco, S., Modi, D. Consequences of Y chromosome microdeletions beyond male infertility. J Assist Reprod Genet 36, 1329–1337 (2019). https://doi.org/10.1007/s10815-019-01492-z

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