Impaired fertility in 4930590J08Rik mutant male mice is associated with defective sperm energy metabolism

Testis-specifically expressed genes are important for male reproduction according to their unique expression patterns. However, the functions of most of these genes in reproduction are unclear. Here, we showed that mouse 4930590J08Rik was a testis-specifically expressed gene. 4930590J08Rik knockout mice exhibited a delay in the first wave of spermatogenesis and a reduction of cauda epididymal sperm. Furthermore, knockout spermatozoa exhibited defective acrosome reactions and decreased progressive motility, which led to impaired in vivo fertilization. Transcriptome analysis of testes revealed that most of the differentially expressed genes in knockout testes were associated with metabolic processes. 4930590J08Rik knockout sperm exhibited oxidative phosphorylation deficiency and were highly dependent on increased anaerobic glycolysis to compensate for ATP demands. Taken together, the 4930590J08Rik-disrupted mouse partially mimics the phenotypes of human asthenospermia and oligozoospermia, which provides a new model for further understanding the pathogenesis of idiopathic male infertility.

Automated summary

The testis-specific gene 4930590J08Rik plays a crucial role in male reproduction, as evidenced by its unique expression pattern and the phenotypes observed in knockout mice. This gene disruption leads to impairment in spermatogenesis, reduced sperm count, defective acrosome reactions, and decreased sperm motility. The transcriptome analysis of testes from knockout mice revealed metabolic dysregulation, specifically oxidative phosphorylation deficiency and increased reliance on anaerobic glycolysis. These findings provide novel insights into idiopathic male infertility and present 4930590J08Rik knockout mice as a valuable model for further investigations.