Absence of annulus in human asthenozoospermia: case report.
The annulus is a septin-based ring structure located at the junction of the midpiece (MP) and the principal piece (PP) of spermatozoa flagellum. In the mouse, deletion of Septin 4, a structural component of the sperm annulus, prevents annulus formation and leads to MP-PP disjunction, flagellar bending, asthenozoospermia and male sterility. Testis anion transporter 1 (Tat1) is a germ cell-specific member of the SLC26 anion transporter family and is co-expressed with Septin 4 at the sperm annulus. Interestingly, Tat1 null sperm bear an atrophic annulus, causing a phenotype similar to that of Sept4 null sperm. We searched for Tat1 misexpression and/or mislocalization in spermatozoa from asthenozoospermic subjects (n = 75) and controls by performing an immunofluorescence detection assay on sperm smear preparations. We found one patient showing moderate asthenozoospermia, with 97% of sperm lacking Tat1, Septin 4 and Septin 7 proteins at the annulus. We confirmed the absence of the annulus structure by transmission electron microscopy and observed that spermatozoa from the patient displayed MP-PP disjunction and abnormal mitochondrial organization. We show that the structural defects in sperm are not caused by abnormal transcription or point mutations of the TAT1 and SEPT4 genes; however, although both proteins are expressed, they are not properly localized at sperm annulus. The case we studied, so far unreported in human, confirms the involvement of Tat1 and Septin proteins in the constitution of the annulus, but also raises questions about the function of this structure in human sperm motility.
Lhuillier
P
P
Département Génétique et Développement, Institut Cochin, 24 rue du faubourg Saint-Jacques, Paris 75014, France.
Rode
B
B
Escalier
D
D
Lorès
P
P
Dirami
T
T
Bienvenu
T
T
Gacon
G
G
Dulioust
E
E
Touré
A
A
D000328:Adult; D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics* / Q000378:metabolism; D017920:Antiporters / Q000235:genetics* / Q000378:metabolism; D053627:Asthenozoospermia / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D017354:Point Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058112:Septins; D013081:Sperm Motility / Q000502:physiology; D013082:Sperm Tail / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure; D000076988:Sulfate Transporters
D027321:Anion Transport Proteins; D017920:Antiporters; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C455627:SLC26A8 protein, human; D000076988:Sulfate Transporters; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C502729:SEPTIN12 protein, human; C492027:SEPTIN4 protein, human; C436485:SEPTIN6 protein, human; C113158:SEPTIN7 protein, human; D058112:Septins