OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis

doi:10.1038/srep37205

CNU IR > College of Sustainable Environment and Recreation > Dept. of Recreation and Health-Care Management > Periodical Articles > Item 310902800/31060

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Title:	OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis
Authors:	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
Contributors:	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
Keywords:	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
Date:	2016-11
Issue Date:	2018-01-18 11:40:50 (UTC+8)
Publisher:	Nature Publishing Group
Abstract:	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.
Relation:	Scientific Reports, v.6, 37205
Appears in Collections:	[Dept. of Recreation and Health-Care Management] Periodical Articles

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