The expression level of septin12 is critical for spermiogenesis.
Septins belong to a family of polymerizing GTP-binding proteins that are required for many cellular functions, such as membrane compartmentalization, vesicular trafficking, mitosis, and cytoskeletal remodeling. One family member, septin12, is expressed specifically in the testis. In this study, we found septin12 expressed in multiple subcellular compartments during terminal differentiation of mouse germ cells. In humans, the testicular tissues of men with either hypospermatogenesis or maturation arrest had lower levels of SEPTIN12 transcripts than normal men. In addition, increased numbers of spermatozoa with abnormal head, neck, and tail morphologies lacked SEPT12 immunostaining signals, as compared with normal spermatozoa. To elucidate the role of septin12, we generated 129 embryonic stem cells containing a septin12 mutant allele with a deletion in the exons that encode the N-terminal GTP-binding domain. Most chimeras derived from the targeted embryonic stem cells were infertile, and the few fertile chimeras only produced offspring with a C57BL/6 background. Semen analysis of the infertile chimeras showed a decreased sperm count, decreased sperm motility, and spermatozoa with defects involving all subcellular compartments. The testicular phenotypes included maturation arrest of germ cells at the spermatid stage, sloughing of round spermatids, and increased apoptosis of germ cells. Electron microscopic examination of spermatozoa showed misshapen nuclei, disorganized mitochondria, and broken acrosomes. Our data indicate that Septin12 expression levels are critical for mammalian spermiogenesis.
Lin
Ying-Hung
YH
Graduate Institute of Basic Medical Sciences, National Cheng Kung University, College of Medicine, Tainan, Taiwan.
Lin
Yung-Ming
YM
Wang
Ya-Yun
YY
Yu
I-Shing
IS
Lin
Yi-Wen
YW
Wang
Yun-Han
YH
Wu
Ching-Ming
CM
Pan
Hsien-An
HA
Chao
Shin-Chih
SC
Yen
Pauline H
PH
Lin
Shu-Wha
SW
Kuo
Pao-Lin
PL
D000177:Acrosome / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053627:Asthenozoospermia / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D007248:Infertility, Male / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008540:Meiosis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055101:Semen Analysis; D058112:Septins; D013087:Spermatids / Q000378:metabolism; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000378:metabolism*
D010446:Peptide Fragments; D012333:RNA, Messenger; D019204:GTP-Binding Proteins; C502729:SEPTIN12 protein, human; C524796:Septin12 protein, rat; D058112:Septins