Subrini, Jeremie Lucas;
(2024)
The role of Y-chromosome genes in mouse spermatogenesis.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
Thesis_Subrini_final.pdf - Other Download (7MB) | Preview |
Abstract
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.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The role of Y-chromosome genes in mouse spermatogenesis |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10186125 |
Archive Staff Only
 |
View Item |
