| First Author | Liu YL | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 37205 | PubMed ID | 27853306 |
| Mgi Jnum | J:250169 | Mgi Id | MGI:6101716 |
| Doi | 10.1038/srep37205 | Citation | Liu YL, et al. (2016) OSR1 and SPAK cooperatively modulate Sertoli cell support of mouse spermatogenesis. Sci Rep 6:37205 |
| abstractText | 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. |
