Fbxw17 is dispensable for viability and fertility in mice.

BACKGROUND: Skp1-Cullin-F-box (SCF) E3 ligase complex plays an important role in regulating spermatogenesis and fertility in mice. As a member of F-box proteins, the function of F-box and WD-40 domain protein 17 (Fbxw17) during spermatogenesis and fertility is unclear. In this study, we illustrate its function for spermatogenesis and fertility. METHODS AND RESULTS: Here, we generated the Fbxw17 knockout (KO) mouse model by using the CRISPR/Cas9 system and analyzed the meiotic process and the fertility. Then, our results demonstrated that testis and sperm in the Fbxw17 KO mice had normal morphology. The testis weight, sperm count and fertility of Fbxw17 KO mice showed no significant difference compared with the wild-type mice. Subsequently, histological analysis of Fbxw17 KO mice revealed apparently normal germ cells of all stages and mature spermatozoa. Meanwhile, nuclear spread analysis showed that the synaptonemal complex formation and DSB repair proceeded normally in Fbxw17-deficient spermatocytes. Furthermore, we didn't find defects in the meiotic prophase I spermatocytes and germ cells showed no apparent apoptosis in Fbxw17 KO mice. CONCLUSIONS: Our results show that Fbxw17 is dispensable for fertility in mice.

PWWP3A deficiency accelerates testicular senescence in aged mice.

BACKGROUND: The PWWP domain-containing proteins are involved in chromatin-associated biological processes, including transcriptional regulation and DNA repair, and most of them are significant for gametogenesis and early embryonic development in mammals. PWWP3A, one of the PWWP domain proteins, is a reader of H3K36me2/H3K36me3 and a response factor to DNA damage. However, the physiological role of PWWP3A in spermatogenesis and fertility remains unclear. OBJECTIVE: The goal of this study was to explore the function and mechanism of PWWP3A in the process of spermatogenesis. MATERIALS AND METHODS: We generated V5-Pwwp3a KI mice and PWWP3A polyclonal antibody to observe the localization of PWWP3A in vivo. Meanwhile, Pwwp3a KO mice was used to explore the function in spermatogenesis. RESULTS: We reported that PWWP3A is a predominant expression in the testis of mice. During spermatogenesis, PWWP3A exhibits the temporal expression from early-pachytene to the round spermatids. The results of spermatocyte spreading and immunostaining showed that PWWP3A aggregated on the XY body, which then diffused as the XY chromosome separated at late-diplotene. Although the depletion of PWWP3A had no obvious reproductive defects in young male mice, there were observed morphological abnormalities in sperm heads. Immunoprecipitation demonstrated the interaction of PWWP3A with DNA repair proteins SMC5/6; however, PWWP3A deficiency did not result in any meiotic defects. Notably, the testes of aged male Pwwp3a KO mice displayed pronounced degeneration, and were characterized by the presence of vacuolated seminiferous tubules. Furthermore, RNA-seq analysis revealed an upregulation in the expression of genes which may be involving in immunoregulatory and inflammatory response pathways in aged Pwwp3a KO mice with testicular degeneration. CONCLUSIONS: Our study showed that PWWP3A was highly enriched in the mouse testis, and the Pwwp3a KO mice were fertile. However, the aged Pwwp3a KO male mice displayed testicular atrophy that may be due to changes in the immune micro-environment or abnormal repair of DNA damage.

Loss of Cep72 affects the morphology of spermatozoa in mice.

The centrosome regulates mammalian meiosis by affecting recombination, synapsis, chromosome segregation, and spermiogenesis. Cep72 is one of the critical components of the centrosome. However, the physiological role of Cep72 in spermatogenesis and fertility remains unclear. In this study, we identify Cep72 as a testis-specific expression protein. Although Cep72 knockout mice were viable and fertile, their sperms were morphologically abnormal with incomplete flagellum structures. Transcriptome analysis reveals significant differences in six genes (Gm49527, Hbb-bt, Hba-a2, Rps27a-ps2, Gm29647, and Gm8430), which were not previously associated with spermatogenesis. Overall, these results indicate that Cep72 participates in regulating sperm morphology and yet is dispensable for fertility in mice.