Systematic identification of Y-chromosome gene functions in mouse spermatogenesis
Jeremie Subrini, Wazeer Varsally, Irina Balaguer Balsells, Maike Bensberg, Georgios Sioutas, Obah A. Ojarikre, Valdone Maciulyte, Björn Gylemo, Katharine Crawley, Katherine Courtis, Dirk G. de Rooij, James M. A. Turner
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.