SEPT12-NDC1 Complexes Are Required for Mammalian Spermiogenesis

Area of Science:

• Reproductive Biology
• Cell Biology
• Genetics

Background:

• Male factor infertility affects 50% of infertile couples, with causes including sperm defects.
• SEPTIN12 (SEPT12) is essential for sperm morphology, and its mutations cause oligozoospermia or teratozoospermia.
• NDC1 transmembrane nucleoporin (NDC1) is vital for nuclear pore complex assembly and nuclear morphology.

Purpose of the Study:

• To investigate the functional role of SEPT12-NDC1 complexes in mammalian spermiogenesis.
• To understand the interaction between SEPT12 and NDC1 during sperm development.
• To elucidate the impact of SEPT12-NDC1 interactions on sperm structure and male fertility.

Main Methods:

• Utilized knockout and knock-in mouse models.
• Employed yeast two-hybrid system to identify protein interactors.
• Performed co-immunoprecipitation in male germ cell lines.
• Analyzed protein localization in human spermatozoa and murine sperm using microscopy.

Main Results:

• SEPT12 and NDC1 colocalize in the centrosome regions of human sperm.
• NDC1 localizes to the nuclear membrane and sperm neck during murine spermiogenesis.
• NDC1 overexpression disrupts SEPT12 localization and filament formation.
• Mutated SEPT12 in mice alters NDC1 distribution, impacting sperm morphology.

Conclusions:

• SEPT12-NDC1 complexes play a significant role in mammalian spermiogenesis.
• Dysregulation of SEPT12-NDC1 interaction contributes to sperm structural abnormalities and male infertility.
• Understanding this complex is key to addressing causes of male factor infertility.