| First Author | Miyamoto Y | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 12 | Pages | 16224-16242 |
| PubMed ID | 33058343 | Mgi Jnum | J:303081 |
| Mgi Id | MGI:6511551 | Doi | 10.1096/fj.202000768RR |
| Citation | Miyamoto Y, et al. (2020) Genetic loss of importin alpha4 causes abnormal sperm morphology and impacts on male fertility in mouse. FASEB J 34(12):16224-16242 |
| abstractText | Importin alpha proteins play a central role in the transport of cargo from the cytoplasm to the nucleus. In this study, we observed that male knock-out mice for importin alpha4, which is encoded by the Kpna4 gene (Kpna4(-/-) ), were subfertile and yielded smaller litter sizes than those of wild-type (WT) males. In contrast, mice lacking the closely related importin alpha3 (Kpna3(-/-) ) were fertile. In vitro fertilization and sperm motility assays demonstrated that sperm from Kpna4(-/-) mice had significantly reduced quality and motility. In addition, acrosome reaction was also impaired in Kpna4(-/-) mice. Transmission electron microscopy revealed striking defects, including abnormal head morphology and multiple axoneme structures in the flagella of Kpna4(-/-) mice. A five-fold increase in the frequency of abnormalities in Kpna4(-/-) mice compared to WT mice indicates the functional importance of importin alpha4 in normal sperm development. Moreover, Nesprin-2, which is a component of the linker of nucleus and cytoskeleton complex, was expressed at lower levels in sperm from Kpna4(-/-) mice and was localized with abnormal axonemes, suggesting incorrect formation of the nuclear membrane-cytoskeleton structure during spermiogenesis. Proteomics analysis of Kpna4(-/-) testis showed significantly altered expression of proteins related to sperm formation, which provided evidence that genetic loss of importin alpha4 perturbed chromatin status. Collectively, these findings indicate that importin alpha4 is critical for establishing normal sperm morphology in mice, providing new insights into male germ cell development by highlighting the requirement of importin alpha4 for normal fertility. |
