SEPT14 complexes maintain sperm morphogenesis and function

Mutations in the septin (SEPT) family lead to male infertility. Septin 14 (SEPT14) is abundantly expressed in the testis, and its expression is significantly reduced in individuals with teratozoospermia, suggesting that SEPT14 may play a role in spermatogenesis. Here, we demonstrated that Sept14 is expressed mainly at the acroplaxome, manchette, neck, and annulus during spermiogenesis. To study the role of SEPT14 in sperm morphogenesis and function, the Sept14 knockout (Sept14^-/-) mice were generated. The Sept14^-/- male mice were subfertile and presented phenotypes such as irregular acrosomes, DNA damage, disorganized mitochondria, and displaced annuli. These abnormalities contributed to reduced sperm motility and impaired capacitation. Mechanistically, in the sperm head, SEPT14 interacted and colocalized with microtubules and actin during the manchette formation at the sperm metamorphosis phase. In the annulus, SEPT14 interacted with SEPT9, SEPT7, and SEPT2 to form the septin filaments to maintain the localization of the annulus. The GTP-binding domain (GBD) of SEPT14 interacted with the GBD of SEPT2, whereas the C-terminus of SEPT14 interacted with the GBD of SEPT7. Thus, our study reveals a role of SEPT14 in mediating sperm morphogenesis.