フッ化物曝露は精巣の主要タンパク質発現を低下させることで精子べん毛の超構造を変化させる

Fluoride exposure alters the ultra-structure of sperm flagellum via reducing key protein expressions in testis.

• Chen Liang
• Yuyang He
• Yu Liu
• Yan Gao
• Yongli Han
• Xiang Li
• Yangfei Zhao
• Jundong Wang
• Jianhai Zhang

抄録

飲料水を介したフッ化物（F）の過剰摂取は、ヒトや動物の造精機能を阻害し、精子の質を低下させた。しかし、フッ化物が精子の質に及ぼす影響が、精子の数よりも精子の運動性に焦点を当てたものである理由はまだ明らかにされていない。本研究の目的は、精子べん毛の構造や機能の変化と環境中のフッ化物曝露との間に潜在的な関係を調べることである。40匹の雄性マウスを4群に分け、それぞれ0,25,50,100mg/L NaF脱イオン水で8週間継続的に処理した。精巣の形態、精子べん毛の線維鞘と軸糸の超構造、および11の主要機能遺伝子Akap3, Akap4, Dnah1, Eno4, Cfap43, Cfap44, Hydin, Spef2, Spag6, Spag16, Cfap69について、それぞれ組織学的、透過型電子顕微鏡法、およびリアルタイムPCR法により検討した。その結果、フッ化物はマウス精巣の精子鞭毛の繊維状鞘や軸索を含む典型的な"9+2″微小管構造を損傷することが明らかになった。さらに、繊維状鞘形成に関連するAKAP3とAKAP4のmRNAとタンパク質発現レベル、および軸索のCFAP43, CFAP44とHYDINの発現レベルがフッ化物曝露により低下した。以上のことから、フッ化物が精子べん毛の繊維状鞘や軸索の構造を変化させ、AKAP3, AKAP4, CFAP43, CFAP44, HYDINのmRNAとタンパク質発現レベルを低下させることが明らかになり、フッ化物が精子の質や男性生殖機能を低下させる原因の一つとなっている可能性が示唆された。

Excessive fluoride (F) ingestion via drinking water interfered with spermatogenesis and lowered sperm quality of human and animals. However, it is still unclear why the effects of fluoride on sperm quality focus on mostly sperm motility rather than sperm count. The objective of this study is to investigate the potential relationship between alteration in the structure and function of sperm flagellum and fluoride exposure in the environment. 40 male mice were allocated to four groups which were treated with 0, 25, 50, 100 mg/L NaF deionized water, respectively, for 8 weeks continuously. The testicular morphology, ultra-structure of fibrous sheath and axoneme of sperm flagellum, and eleven key function genes Akap3, Akap4, Dnah1, Eno4, Cfap43, Cfap44, Hydin, Spef2, Spag6, Spag16, and Cfap69 were examined by histology, transmission electron microscopy, and real-time PCR methods respectively. The results displayed that fluoride damaged the typical "9 + 2″ microtubule structure including fibrous sheathes and axoneme of sperm flagellum in testes of mice. Furthermore, the mRNA and protein expression levels of AKAP3 and AKAP4 related to fibrous sheathes formation, and CFAP43, CFAP44 and HYDIN in axoneme were down-regulated by fluoride exposure. Taken together, we revealed that fluoride altered the structures of the fibrous sheathes and axonemal in sperm flagellum via down-regulating the mRNA and protein expression levels of AKAP3, AKAP4, CFAP43, CFAP44, and HYDIN, which may be one of the reasons that fluoride lowered sperm quality and male reproductive function.

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