WSB1 is dispensable for mouse spermatogenesis and male fertility.

PURPOSES: WSB1 (WD repeat and SOCS box-containing protein 1) is part of the E3 ligase complex Elongin B/C-Cullin 2/5-SOCS box E3 ubiquitin ligase (ESC) complex. Our previous studies and those of others have confirmed that some SOCS box proteins, including ASB1 and ASB9, are important for the development of male germ cells. Given that WSB1 is a member of the same protein family, we hypothesized that it might also be involved in spermatogenesis. Although WSB1 has been implicated in tumorigenesis and cancer progression in other tissues due to its E3 ligase activity, its roles and mechanisms in spermatogenesis remain unknown.

METHODS: Conditional knockout (cKO) mice with deletion of the Wsb1 gene were generated using CRISPR/Cas9 genome editing. Sperm quality was analyzed using a computer-assisted sperm analysis (CASA) system. To assess the impact of WSB1 deletion, cauda epididymal sperm morphology and testicular tissue structure and organization were studied. Apoptotic cells in the testes were assessed using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL).

FINDINGS: Compared with wild-type (WT) mice, Wsb1-cKO mice showed no significant differences in fertility, semen quality, tissue morphology, or rates of apoptosis of germ cells. Nevertheless, Wsb2 was distinctly upregulated. These findings suggest that normal male reproduction does not depend on WSB1 and that increased WSB2 may represent a compensatory mechanism due to the loss of WSB1. This compensatory effect may explain the absence of an overt phenotype and may guide future research by focusing on other candidate genes and providing context for studies in human reproductive genetics.