Oral Virtual Presentation (Virtual only) ESA-SRB-ANZBMS 2021

Epsilon tubulin is required for fertility in male mice and has essential roles in meiosis and spermatid remodelling (#115)

Gemma Stathatos 1 , Jo Merriner 1 , Anne O'Connor 1 , Jessica Dunleavy 1 , Jennifer Zenker 2 , Moira O'Bryan 1
  1. The University of Melbourne, Parkville, VIC, Australia
  2. Australian Regenerative Medicine Institute, Monash Univeristy, Clayton, Victoria, Australia

As essential components of the cytoskeleton, alpha, beta and gamma tubulin have deservedly garnered significant research attention. In contrast, their close relative, epsilon tubulin (TUBE1), has received little attention, but promises to be equally as important. Recently, we have shown epsilon tubulin is enriched during male meiosis and spermiogenesis and have identified it as a candidate target for katanin-mediated regulation of the manchette1. Therefore, we set out to investigate epsilon tubulin’s function in spermatogenesis and understand its mechanism of action.

Using Stra8-Cre, we generated a pre-meiotic, male germ cell knockout of epsilon tubulin (Tube1GCKO/GCKO) and found male mice to be sterile. Within these males, testicular sperm production and epididymal sperm content was reduced by 80% and 92% respectively. A closer examination of male germ cells revealed epsilon tubulin is required for spindle microtubule organization and cytokinesis during meiosis. Epsilon tubulin is also required for nuclear remodelling in haploid male germ cells, as evidenced by dysregulated manchettes in Tube1GCKO/GCKO spermatids and the formation of spermatozoa with hyper-constricted nuclei. Moreover, of the reduced numbers of Tube1GCKO/GCKO sperm produced, their swimming ability was significantly compromised, suggesting epsilon tubulin is needed for sperm tail development and/or function. Consistent with our hypothesis that TUBE1 is a target of katanin action, the phenotypes in Tube1GCKO/GCKO mice are reminiscent to those seen in our KATNAL2 and KATNB1 mutant mouse models1, 2. Overall, our results demonstrate epsilon tubulin is indispensable for spermatogenesis, and plays a role in multiple aspects of germ cell development.

1Dunleavy, J.E.M., et al., Katanin-like 2 (KATNAL2) functions in multiple aspects of haploid male germ cell development in the mouse. PLOS Genetics, 2017. 13(11).

2O'Donnell, L., et al., An essential role for katanin p80 and microtubule severing in male gamete production.PLOS Genetics, 2012. 8(5): p. e1002698.