• PMID: 27853306
• Gene Name: OSR1
• Condition: Important for Spermatogenesis, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Important for Spermatogenesis, Male infertility

OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis

Liu YL, Yang SS, Chen SJ, Lin YC, Chu CC, Huang HH, Chang FW, Yu MH, Lin SH, Wu GJ, Sytwu HK.

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. FAU - Liu, Yung-Liang AU - Liu YL AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan. AD - Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. AD - Department of Obstetrics and Gynecology, Tri-Service General Hospital Penghu Branch, Penghu 880, Taiwan. FAU - Yang, Sung-Sen AU - Yang SS AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan. AD - Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. FAU - Chen, Shyi-Jou AU - Chen SJ AD - Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 114, Taiwan. AD - Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. FAU - Lin, Yu-Chun AU - Lin YC AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan. AD - Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. FAU - Chu, Chin-Chen AU - Chu CC AD - Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan. AD - Department of Recreation and Health-Care Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan. FAU - Huang, Hsin-Hui AU - Huang HH AD - Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. FAU - Chang, Fung-Wei AU - Chang FW AD - Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. FAU - Yu, Mu-Hsien AU - Yu MH AD - Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. FAU - Lin, Shih-Hua AU - Lin SH AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan. AD - Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. FAU - Wu, Gwo-Jang AU - Wu GJ AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan. AD - Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.