title: OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis.
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.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.|Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.|Department of Obstetrics and Gynecology, Tri-Service General Hospital Penghu Branch, Penghu 880, Taiwan.
authors.forename: Yung-Liang
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.|Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Sung-Sen
authors.initials: SS
authors.lastname: Yang
authors.affiliation: Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 114, Taiwan.|Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Shyi-Jou
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.|Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan.|Department of Recreation and Health-Care Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Chu
authors.affiliation: Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Hsin-Hui
authors.initials: HH
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Fung-Wei
authors.initials: FW
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Mu-Hsien
authors.initials: MH
authors.lastname: Yu
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.|Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Shih-Hua
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.|Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Gwo-Jang
authors.initials: GJ
authors.lastname: Wu
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.|Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 114, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D008297:Male; D008540:Meiosis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012708:Sertoli Cells / Q000166:cytology / Q000201:enzymology*; D013091:Spermatogenesis / Q000502:physiology*
chemical_list: C486407:Stk39 protein, mouse; C534421:OXSR1 protein, mouse; D017346:Protein Serine-Threonine Kinases