Browsing by Author "Alpaugh, Whitney"

Now showing 1 - 1 of 1
  • Thumbnail Image
    ItemOpen Access
    The role of UCH-L1 in mouse progenitor spermatogonia
    (2016) Alpaugh, Whitney; Dobrinski, Ina; Thundathil, Jacob; Natale, David; van der Hoorn, Frans; Ungrin, Mark
    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.