The role of UCH-L1 in mouse progenitor spermatogonia

To maintain fertility throughout the life of the adult male, the spermatogonial stem cell (SSC) population of the testis needs to achieve a balance between self-renewal and differentiation. The chemical, molecular and physical environment that supports this balance of fate decision is not completely understood. The deubiquitinating enzyme Ubiquitin C-terminal Hydrolase L1 (UCH-L1) is highly expressed in spermatogonia, but not in further differentiating germ cells of the testis. Previous studies have shown that UCH-L1 is important for normal spermatogenesis; however, its specific role has not been determined. The experiments in this thesis establish that UCH-L1 is specifically expressed in undifferentiated and early differentiating mouse spermatogonia. Examination of the Uch-l1-/- testis revealed that, as mice age, there is an increase in the number of degenerating tubules as well as a decrease in numbers of differentiating cells in the absence of UCH-L1. A combination of gene expression data and analysis of donor-derived spermatogenesis after transplantation of Uch-l1-/- SSCs to germ celldepleted wild-type recipient testes demonstrated that over time, in the absence of UCHL1, the spermatogonia pool expands at the expense of differentiation. Additionally, RNA sequencing of Uch-l1+/+ and Uch-l1-/- spermatogonia showed that the Uch-l1-/- spermatogonia have a gene expression profile closer to that of undifferentiated spermatogonia than to that of differentiating spermatogonia. Finally, 31 novel binding partners for UCH-L1 were identified in spermatogonia which provides a starting point for identifying the mechanisms through which UCH-L1 acts to affect spermatogonia fate decision.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Grantor dc:publisher.institution

Graduate Studies

Year dc:date.issued

2016

Author dc:creator

• Alpaugh, Whitney

Advisors dc:contributor.advisor

• Dobrinski, Ina
• Thundathil, Jacob

Committee members dc:contributor.committeemember

• Natale, David
• van der Hoorn, Frans
• Ungrin, Mark

• Biology--Cell

Statement dc:rights

• University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.

Language dc:language.iso

eng

DOI

http://dx.doi.org/10.11575/PRISM/28367

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:11023/3516