• PMID: 19359518
• Gene Name: SEPTIN12
• Condition: Spermiogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility

The expression level of septin12 is critical for spermiogenesis

Lin YH, Lin YM, Wang YY, Yu IS, Lin YW, Wang YH, Wu CM, Pan HA, Chao SC, Yen PH, Lin SW, Kuo PL.

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. FAU - Lin, Ying-Hung AU - Lin YH AD - Graduate Institute of Basic Medical Sciences, National Cheng Kung University, College of Medicine, Tainan, Taiwan. FAU - Lin, Yung-Ming AU - Lin YM FAU - Wang, Ya-Yun AU - Wang YY FAU - Yu, I-Shing AU - Yu IS FAU - Lin, Yi-Wen AU - Lin YW FAU - Wang, Yun-Han AU - Wang YH FAU - Wu, Ching-Ming AU - Wu CM FAU - Pan, Hsien-An AU - Pan HA FAU - Chao, Shin-Chih AU - Chao SC FAU - Yen, Pauline H AU - Yen PH FAU - Lin, Shu-Wha AU - Lin SW