2021 Fiscal Year Final Research Report

Molecular cytological clarification of pathogenesis of male infertility by analyzing genetically modified animals and its clinical application

Research Project

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Project/Area Number	19K09665
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56030:Urology-related
Research Institution	Chiba University
Principal Investigator	Ito Chizuru 千葉大学, 大学院医学研究院, 講師 (80347054)
Co-Investigator(Kenkyū-buntansha)	武藤透千葉大学, 大学院医学研究院, 技術専門職員 (30422265)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	男性不妊症 / 遺伝子改変マウス / 遺伝子欠損雄性不妊モデルマウス / 中心体関連タンパク質 / ODF2 / DDS-頭部離断精子 / ODF4 / ヘアピン鞭毛精子
Outline of Final Research Achievements	Odf2 haploinsufficiency induces sperm neck-midpiece separation, a new type of decapitated and decaudated spermatozoa (DDS). DDS is untreatable in reproductive medicine.The headnecks of ODF2-DDS spermatozoa are, however, alive and capable of producing offspring by intracytoplasmic headneck sperm injection (ICSI). ICSI in humans, using headneck sperm cells, is viable and could be an alternative for infertile patients suffering from Odf2-DDS（Ito et al, Sci.Rep.,2019). Odf4 knockout male mice are infertile. Their spermatozoa progress backward and fail to ascend in the uterus owing to bent (hairpin) flagellum caused by failure to remove huge residual cytoplasmic droplets. Bent flagellum is one of the most common disorders in sperm shaping and movement in male infertile patients. Our further study will open a new window to understanding the mechanism of bent flagellum and it's medical treatment.
Free Research Field	生殖生物医学
Academic Significance and Societal Importance of the Research Achievements	頭部離断精子(DDS)は死滅と診断され治療に使われないが、Odf2遺伝子のハプロ不全が原因のDDSは、精子頸部-中間部間で断裂する新しく発見したタイプのDDSであり顕微授精によって治療できる。ヒトにおいてOdf2-DDSが診断できれば、離断した精子を使うことで治療の道が開けることを明らかにした。Odf4遺伝子欠損マウスの精子は、不妊患者でもよく観察される尾部の屈曲変形（ヘアピン鞭毛）を示す。現在、屈曲変形の生じる詳細なメカニズムを解析中であり、その情報は生殖補助医療に活用できると考えられる。