The expression level of septin12 is critical for spermiogenesis

Ying Hung Lin, Yung Ming Lin, Ya Yun Wang, I. Shing Yu, Yi Wen Lin, Yun Han Wang, Ching Ming Wu, Hsien An Pan, Shin Chih Chao, Pauline H. Yen, Shu Wha Lin, Pao Lin Kuo

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1857-1868
Number of pages12
JournalAmerican Journal of Pathology
Volume174
Issue number5
DOIs
Publication statusPublished - 2009 May

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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