The Potential Role of Deubiquitinating Enzymes (DUBs) in Male Fertility

Ubiquitination dynamically regulates critical cellular processes, including cell cycle progression, apoptosis, DNA repair, and chromatin remodeling. Deubiquitinating enzymes (DUBs) negatively regulate protein ubiquitination and are equally important for protein regulation in diverse biological processes. Spermatogenesis is a highly regulated process involving spermatogonia self-renewal and differentiation, ensuring continuous sperm production. Using a loss-of-function mouse model, several DUBs have been shown to be involved in spermatogenesis. In addition, specific genetic variants in the DUB genes have been associated with spermatogenic failure and male infertility. These studies provide strong evidence that DUBs are necessary for normal spermatogenesis and may influence male fertility. However, the exact mechanism by which these DUBs regulate spermatogenesis is still under investigation. The aim of this review is to highlight recent advances in the regulatory roles of DUBs in mammalian spermatogenesis and provide insight into the molecular mechanisms underlying their potential actions. An in-depth understanding of DUB-mediated regulation of spermatogenesis will provide a scientific rationale for the discovery and development of novel DUB-targeted therapeutic strategies for male infertility.