Male infertility, impaired sperm motility, and hydrocephalus in mice deficient in sperm-associated antigen 6

Area of Science:

• Reproductive biology
• Developmental biology
• Cell biology

Background:

• Sperm flagellar motility is essential for male fertility.
• The axoneme central apparatus plays a critical role in flagellar function.
• Sperm-associated antigen 6 (Spag6) is an axonemal protein with predicted roles in motility and stability.

Purpose of the Study:

• To investigate the function of Spag6 in vivo.
• To determine the role of Spag6 in sperm motility and flagellar structure.
• To assess the potential involvement of Spag6 in other ciliary functions.

Main Methods:

• Gene targeting was employed to generate Spag6-deficient mice.
• Phenotypic analysis included survival rates, fertility assessment, and sperm morphology/motility evaluation.
• Histological examination of sperm flagella and analysis of ependymal cilia were performed.

Main Results:

• Spag6-deficient mice exhibited hydrocephalus and high mortality rates within 8 weeks of birth.
• Mature Spag6-deficient males were infertile with severely impaired sperm motility and abnormal morphology.
• Sperm flagella showed structural defects, including loss of central microtubules and disorganization of outer dense fibers and fibrous sheath.

Conclusions:

• Spag6 is essential for maintaining sperm flagellar motility and structural integrity.
• Spag6 plays a critical role in the stability of the axoneme central apparatus.
• The study implicates Spag6 in ependymal cilia motility, suggesting a broader role in ciliary function.