Systematic identification of Y-chromosome gene functions in mouse spermatogenesis

Jeremie Subrini; Wazeer Varsally; Irina Balaguer Balsells; Maike Bensberg; Georgios Sioutas; Obah Ojarikre; Valdone Maciulyte; Björn Gylemo; Katharine Crawley; Katherine Courtis; Dirk G de Rooij; James M A Turner

doi:10.1126/science.ads6495

Systematic identification of Y-chromosome gene functions in mouse spermatogenesis

Jeremie Subrini, Wazeer Varsally, Irina Balaguer Balsells, Maike Bensberg, Georgios Sioutas, Obah Ojarikre, Valdone Maciulyte, Björn Gylemo, Katharine Crawley, Katherine Courtis, Dirk G de Rooij, James M A Turner^*

^*Corresponding author for this work

The Francis Crick Institute

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The mammalian Y chromosome is essential for male fertility, but which Y genes regulate spermatogenesis is unresolved. We addressed this by generating 13 Y-deletant mouse models. In Eif2s3y, Uty, and Zfy2 deletants, spermatogenesis was impaired. We found that Uty regulates spermatogonial proliferation, revealed a role for Zfy2 in promoting meiotic sex chromosome pairing, and uncovered unexpected effects of Y genes on the somatic testis transcriptome. In the remaining single Y-gene deletants, spermatogenesis appeared unperturbed, but testis transcription was still altered. Multigene deletions, including a human-infertility AZFa model, exhibited phenotypes absent in single Y deletants. Thus, Y genes may regulate spermatogenesis even if they show no phenotypes when deleted individually. This study advances our knowledge of Y evolution and infertility and provides a resource to dissect Y-gene functions in other tissues.

Original language	English
Pages (from-to)	393-400
Number of pages	8
Journal	Science (New York, N.Y.)
Volume	387
Issue number	6732
DOIs	https://doi.org/10.1126/science.ads6495
Publication status	Published - 24 Jan 2025

Keywords

Animals
Cell Proliferation
DNA-Binding Proteins/genetics
Eukaryotic Initiation Factor-2/metabolism
Gene Deletion
Genes, Y-Linked
Humans
Infertility, Male/genetics
Male
Meiosis/genetics
Mice
Spermatogenesis/genetics
Spermatogonia/metabolism
Testis/metabolism
Transcription Factors
Transcriptome
Y Chromosome/genetics

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title = "Systematic identification of Y-chromosome gene functions in mouse spermatogenesis",

abstract = "The mammalian Y chromosome is essential for male fertility, but which Y genes regulate spermatogenesis is unresolved. We addressed this by generating 13 Y-deletant mouse models. In Eif2s3y, Uty, and Zfy2 deletants, spermatogenesis was impaired. We found that Uty regulates spermatogonial proliferation, revealed a role for Zfy2 in promoting meiotic sex chromosome pairing, and uncovered unexpected effects of Y genes on the somatic testis transcriptome. In the remaining single Y-gene deletants, spermatogenesis appeared unperturbed, but testis transcription was still altered. Multigene deletions, including a human-infertility AZFa model, exhibited phenotypes absent in single Y deletants. Thus, Y genes may regulate spermatogenesis even if they show no phenotypes when deleted individually. This study advances our knowledge of Y evolution and infertility and provides a resource to dissect Y-gene functions in other tissues.",

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AU - Sioutas, Georgios

AU - Ojarikre, Obah

AU - Maciulyte, Valdone

AU - Gylemo, Björn

AU - Crawley, Katharine

AU - Courtis, Katherine

AU - de Rooij, Dirk G

AU - Turner, James M A

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AB - The mammalian Y chromosome is essential for male fertility, but which Y genes regulate spermatogenesis is unresolved. We addressed this by generating 13 Y-deletant mouse models. In Eif2s3y, Uty, and Zfy2 deletants, spermatogenesis was impaired. We found that Uty regulates spermatogonial proliferation, revealed a role for Zfy2 in promoting meiotic sex chromosome pairing, and uncovered unexpected effects of Y genes on the somatic testis transcriptome. In the remaining single Y-gene deletants, spermatogenesis appeared unperturbed, but testis transcription was still altered. Multigene deletions, including a human-infertility AZFa model, exhibited phenotypes absent in single Y deletants. Thus, Y genes may regulate spermatogenesis even if they show no phenotypes when deleted individually. This study advances our knowledge of Y evolution and infertility and provides a resource to dissect Y-gene functions in other tissues.

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KW - Transcription Factors

KW - Transcriptome

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Systematic identification of Y-chromosome gene functions in mouse spermatogenesis

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