| Summary: | 博士 === 國立成功大學 === 基礎醫學研究所 === 97 === It is estimated that 10- 15% of couples are infertile and male factors account for about half of the cases. About 25% of the causes of male infertility are still unknown and the majority of infertile cases have defects in spermatogenesis. But large of those spermatogenesis are still unknown. To identify novel genes which are involved in mammalian spermatogenesis, we studied global gene expression patterns in testicular biopsies of men with spermatogenic defects by c-DNA microarrays. We found ten novel genes of which transcripts were significantly decreased in patients with Sertoli cell only syndrome or Maturation arrest. Because the transcripts of Septin12 (SEPT12) are specific express in human and mouse testis. We chose Septin12 gene for further study.
Septins belong to a family of polymerizing GTP binding proteins that are required for many cellular functions, including membrane compartmentalization, vesicle trafficking, mitosis and cytoskeletal remodeling. In this study, we found SEPTIN12, one of the SEPTIN family members, is expressed specifically in the testis. SEPT12 expressed in multiple subcellular compartments during terminal differentiation of post-meiotic germ cells. To elucidate the role of Septin12, we generated 129 ES cells with a Septin12 mutant allele deleted in the exons encoding the N-terminal GTP binding domain. Most chimeras derived from the targeted ES cells were infertile. Semen analysis of the infertile chimeras showed decreased sperm counts, 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 acrosome. In humans, the testicular tissues of men with hypo-spermatogenesis or maturation arrest had lower levels of the SEPTIN12 transcripts. In addition, more spermatozoa with abnormal head, neck and tail morphology lacked SEPT12 immunostaining signals compared to spermatozoa with normal appearance. Our data support a critical role of Septin12 during mammalian spermiogenesis.
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