UBA2-Mediated Sumoylation Is Required for Both Spermatocyte and Sertoli Cell Functions During Mouse Spermatogenesis

SUMO proteins are highly expressed in testicular cells, including spermatocytes and Sertoli, where they modify numerous proteins. Nonetheless, the role of SUMO proteins in spermatogenesis in vivo has remained unconfirmed.

To confirm the requirement for sumoylation in the mouse in vivo during meiosis and in testicular Sertoli cells.

To inactivate sumoylation, we targeted the UBA2 gene, a subunit of the only known SUMO-activating enzyme. Stra8-Cre, Amh-Cre, and Uba2^fx/fl mice were used to produce Uba2^fl/fl-Cre mice with the conditional deletion of Uba2 in either early meiotic or Sertoli cells.

Both mouse models have exhibited complete male infertility, a significant decrease in testicular weight, and spermatogenic arrest. Inactivation of sumoylation in spermatocytes led to meiotic arrest and misregulated expression of many genes involved in meiotic completion and spermatid differentiation. Inactivation of sumoylation in Sertoli cells leads to loss of germ cells, progressive testicular degeneration, and misregulated expression of genes that control Sertoli cell function, including those involved in germ cell adhesion and junctional complex formation. Transcription factor WT1 may be an important target of sumoylation in Sertoli cells.

Sumoylation may provide a dual-layer regulatory mechanism through direct binding to proteins required for meiosis and Sertoli cell functions, and indirect control of transcriptional events through regulation of transcription factors and chromatin modifiers. Future studies will address the mechanisms by which sumoylation controls transcription and other events in testicular cells.

UBA2-mediated sumoylation is required for both spermatocyte and Sertoli cell functions.