Systematic identification of Y-chromosome gene functions in mouse spermatogenesis

• 成果类型: Article
• 署名作者: Subrini, Jeremie; Varsally, Wazeer; Balsells, Irina Balaguer; Bensberg, Maike; Sioutas, Georgios; Ojarikre, Obah; Maciulyte, Valdone; Gylemo, Bjoern; Crawley, Katharine; Courtis, Katherine; de Rooij, Dirk G.; Turner, James M. A.
• 署名单位: Francis Crick Institute; Linkoping University; Linkoping University; Francis Crick Institute; Utrecht University; University of Amsterdam; Academic Medical Center Amsterdam
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12816
• DOI: 10.1126/science.ads6495
• 发表日期: 2025-01-24
• 页码: 393-400
• 关键词: embryonic stem-cells; mice; generation; sperm; chromatin; eif2s3y; number; acts; rna

摘要

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.