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    標題: OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis
    作者: Liu, Yung-Liang
    Yang, Sung-Sen
    Chen, Shyi-Jou
    Lin, Yu-Chun
    Chu, Chin-Chen
    Huang, Hsin-Hui
    Chang, Fung-Wei
    Yu, Mu-Hsien
    Lin, Shih-Hua
    Wu, Gwo-Jang
    Sytwu, Huey-Kang
    貢獻者: Natl Def Med Ctr, Grad Inst Med Sci
    Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Obstet & Gynecol
    Tri Serv Gen Hosp, Dept Obstet & Gynecol, Penghu Branch
    Tri Serv Gen Hosp, Natl Def Med Ctr, Div Nephrol, Dept Med
    Natl Def Med Ctr, Dept & Grad Inst Microbiol & Immunol
    Tri Serv Gen Hosp, Dept Pediat, Natl Def Med Ctr
    Tri Serv Gen Hosp, Dept Pathol, Natl Def Med Ctr
    Chi Mei Med Ctr, Dept Anesthesiol
    Chia Nan Univ Pharm & Sci, Dept Recreat & Hlth Care Management
    Natl Def Med Ctr, Grad Inst Life Sci
    關鍵字: transcription factor gata-1
    alanine-rich kinase
    k-cl cotransporter
    smooth-muscle tone
    blood-pressure
    a-myb
    na+-k+-2cl(-) cotransporter
    tyrosine phosphorylation
    mice
    gene
    日期: 2016-11
    上傳時間: 2018-01-18 11:40:50 (UTC+8)
    出版者: Nature Publishing Group
    摘要: We investigated the role of oxidative stress-responsive kinase-1 (OSR1) and STE20 (sterile 20)/SPS1-related proline/alanine-rich kinase (SPAK), upstream regulators of the Na+-K+-2Cl(-) cotransporter (NKCC1)-essential for spermatogenesis-in mouse models of male fertility. Global OSR1(+/-) gene mutations, but not global SPAK(-/-) or Sertoli cell (SC)-specific OSR1 gene knockout (SC-OSR1(-/-)), cause subfertility with impaired sperm function and are associated with reduced abundance of phosphorylated (p)-NKCC1 but increased p-SPAK expression in testicular tissue and spermatozoa. To dissect further in a SC-specific manner the compensatory effect of OSR1 and SPAK in male fertility, we generated SC-OSR1(-/-) and SPAK(-/-) double knockout (DKO) male mice. These are infertile with defective spermatogenesis, presenting a SC-only-like syndrome. Disrupted meiotic progression and increased germ cell apoptosis occurred in the first wave of spermatogenesis. The abundance of total and p-NKCC1 was significantly decreased in the testicular tissues of DKO mice. These results indicate that OSR1 and SPAK cooperatively regulate NKCC1-dependent spermatogenesis in a SC-restricted manner.
    關聯: Scientific Reports, v.6, 37205
    顯示於類別:[休閒保健管理系(所)] 期刊論文

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