The Gene Is Necessary for Spermatozoa Development and Male Fertility in Mice.

gene loss-of-function mutation leads to Primary Ciliary Dyskinesia (PCD), a disease caused by motile cilia dysfunction. Previously, we demonstrated that knockout of the gene in mice replicates several features of PCD, such as hydrocephalus, defects in left-right body symmetry, and male infertility, with a complete absence of sperm in the reproductive tract. The majority of knockout animals die before sexual maturation due to severe hydrocephalus and failure to thrive, which precludes fertility studies. Here, we performed the expression analysis of the gene during gonad development and in adult testes. We showed that starts its expression during the first wave of spermatogenesis, specifically at the meiotic stage, and that its expression is restricted to the germ cells in the adult testes, suggesting that plays a role in spermatozoa formation. Subsequently, we conditionally deleted the gene in adult males and demonstrated that even partial ablation of the gene leads to asthenoteratozoospermia with multiple morphological abnormalities of sperm flagella (MMAF) in mice. The analysis of the seminiferous tubules in -deficient mice revealed defects in spermatogenesis with accumulation of seminiferous tubules at the spermiogenesis and spermiation phases. Furthermore, analysis of fertility in heterozygous knockout mice revealed a reduction in sperm count and motility as well as abnormal sperm morphology. Additionally, males exhibited a shorter fertile lifespan. Overall, these results suggest the important role of and gene dosage in male fertility. These findings may have an impact on the genetic and fertility counseling practice of PCD patients carrying loss-of-function mutations.