OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis

Yung-Liang Liu; Sung-Sen Yang; Shyi-Jou Chen; Yu-Chun Lin; Chin-Chen Chu; Hsin-Hui Huang; Fung-Wei Chang; Mu-Hsien Yu; Shih-Hua Lin; Gwo-Jang Wu; Huey-Kang Sytwu

doi:10.1038/srep37205

OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis

Sci Rep. 2016 Nov 17:6:37205. doi: 10.1038/srep37205.

Authors

Yung-Liang Liu^{1

2

3}, Sung-Sen Yang^{1

4}, Shyi-Jou Chen^{5

6}, Yu-Chun Lin^{1

7}, Chin-Chen Chu^{8

9}, Hsin-Hui Huang², Fung-Wei Chang², Mu-Hsien Yu², Shih-Hua Lin^{1

4}, Gwo-Jang Wu^{1

2}, Huey-Kang Sytwu^{1

5

10}

Affiliations

¹ Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.
² Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
³ Department of Obstetrics and Gynecology, Tri-Service General Hospital Penghu Branch, Penghu 880, Taiwan.
⁴ Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
⁵ Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 114, Taiwan.
⁶ Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
⁷ Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
⁸ Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan.
⁹ Department of Recreation and Health-Care Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
¹⁰ Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / physiology
Male
Meiosis / physiology
Mice
Mice, Knockout
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Sertoli Cells / cytology
Sertoli Cells / enzymology*
Spermatogenesis / physiology*

Substances

Stk39 protein, mouse
OXSR1 protein, mouse
Protein Serine-Threonine Kinases