Absence of annulus in human asthenozoospermia: case report

Area of Science:

• Reproductive Biology
• Spermatozoa Ultrastructure
• Male Fertility Research

Background:

• The sperm annulus, a septin-based ring structure, connects the midpiece and principal piece of the flagellum.
• Septin 4 deficiency in mice disrupts annulus formation, leading to male sterility.
• Testis anion transporter 1 (Tat1) is co-expressed with Septin 4 at the sperm annulus and its absence causes similar phenotypes in mice.

Observation:

• Immunofluorescence analysis of spermatozoa from asthenozoospermic subjects revealed one patient with 97% sperm lacking Tat1, Septin 4, and Septin 7 at the annulus.
• Transmission electron microscopy confirmed the absence of the annulus structure in the patient's sperm.
• The patient's spermatozoa exhibited midpiece-principal piece disjunction and abnormal mitochondrial organization.

Findings:

• The structural defects in the patient's sperm were not due to abnormal gene transcription or point mutations in TAT1 and SEPT4.
• Both Tat1 and Septin proteins were expressed but mislocalized, failing to assemble at the sperm annulus.
• This case represents the first reported human instance linking Tat1 and Septin mislocalization to annulus defects and asthenozoospermia.

Implications:

• Confirms the essential role of Tat1 and Septin proteins in the structural integrity of the human sperm annulus.
• Suggests that annulus defects, due to protein mislocalization, contribute to human male infertility.
• Raises further questions about the specific functions of the sperm annulus in human sperm motility and fertilization.