Rats exhibit age-related mosaic loss of chromosome Y

Journal article

In mammals, male germ cells require Y chromosome genes to successfully complete the three major steps of spermatogenesis: mitosis, meiosis and spermiogenesis. Indeed, in mice and men, chromosomal deletions on the Y are linked to diverse spermatogenic abnormalities throughout gamete development, ultimately causing infertility. However, linking each Y gene to specific aspects of male reproduction has been challenging. As the Y chromosome has been notoriously hard to sequence and target, much remains unknown about “which Y gene does what” during spermatogenesis. This thesis systematically investigates the roles of Y genes in mouse spermatogenesis through the generation and analysis of eleven mouse models with whole Y locus deletions, achieved by CRISPR-Cas9 manipulation of mouse embryonic stem cells followed by tetraploid complementation for mutant mouse generation. Phenotyping was performed in Y deletants by systematically investigating their overall reproductive output, screening for testicular abnormalities, quantifying the number and quality of spermatozoa and characterising their testis transcriptional landscape. I found that most Y genes appear to be dispensable for mouse spermatogenesis, even though many of them show testis-specific expression and deep conservation across mammalian lineages. However, the Zfy gene family emerged as a crucial factor influencing both meiosis and spermatid morphogenesis, and a previously unknown role for Zfy2 in meiotic chromosome pairing was unveiled. Additionally, Uty was discovered to play a role in spermatogonia cell differentiation. Overall, by systematically dissecting the functions of individual Y genes, this research sheds light on long-standing questions regarding the involvement of the Y chromosome in male fertility. This work carries implications for better understanding and addressing human infertility and allows to gain a deeper insight into the evolutionary path of the Y chromosome

Authors: Orta, AH; Bush, SJ; Gutiérrez-Mariscal, M; Castro-Obregón, S; Jaimes-Hoy, L

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Communications Biology
• Volume: 4
• Issue: 1
• Pages: 1418-1418
• Article number: 1418
• Publication date: 2021-12-21
• DOI: 10.1038/s42003-021-02936-y
• EISSN: 2399-3642
• ISSN: 2399-3642
• Language: English
• Keywords: Locus (genetics); Y chromosome; Biology; Gene; Chromosome; Genetics; Genome; X chromosome