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OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis

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 mu...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112561/
https://www.ncbi.nlm.nih.gov/pubmed/27853306
http://dx.doi.org/10.1038/srep37205
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author 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
author_facet 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
author_sort Liu, Yung-Liang
collection PubMed
description 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.
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spelling pubmed-51125612016-11-23 OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis 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 Sci Rep Article 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. Nature Publishing Group 2016-11-17 /pmc/articles/PMC5112561/ /pubmed/27853306 http://dx.doi.org/10.1038/srep37205 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
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
OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis
title OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis
title_full OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis
title_fullStr OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis
title_full_unstemmed OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis
title_short OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis
title_sort osr1 and spak cooperatively modulate sertoli cell support of mouse spermatogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112561/
https://www.ncbi.nlm.nih.gov/pubmed/27853306
http://dx.doi.org/10.1038/srep37205
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