Systematic identification of Y-chromosome gene functions in mouse spermatogenesis.

Subrini, Jeremie; Varsally, Wazeer; Balsells, Irina Balaguer; Bensberg, Maike; Sioutas, Georgios; Ojarikre, Obah; Maciulyte, Valdone; Gylemo, Björn et al. · Science · 2025

basic_science · Level V

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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 <i>Eif2s3y</i>, <i>Uty</i>, and <i>Zfy2</i> deletants, spermatogenesis was impaired. We found that <i>Uty</i> regulates spermatogonial proliferation, revealed a role for <i>Zfy2</i> 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.

Medical subject headings