Relationship between ouabain and asthenozoospermia

  • Yi-hong Yang (杨宜红)
  • Yan Wan (万 艳)
  • Huan Lou (娄 欢)
  • Ting Xue (薛 婷)
  • Ping Su (苏 萍)Email author


A growing number of researches have shown that ouabain can regulate mammalian sperm function and male reproduction by modulating the sperm motility, capacitation and acrosome reaction in vitro. This study further examined the relationship between ouabain and asthenozoospermia. In this study, the rat was intraperitoneally injected with ouabain at different concentrations (low-dose ouabain group: 12.5 μg/kg body weight per day, and high-dose ouabain group: 25 μg/kg body weight per day) for 30 days to establish the asthenozoospermia model. The sperms from 60 males with normal fertility were incubated with ouabain of gradient concentrations (10-7–10-2 mol/L) for 4 h. The sperm motility was evaluated under a microscope. Moreover, the endogenous ouabain (EO) level was determined in seminal plasma of mild or severe asthenozoospermia patients and males with normal fertility by competitive inhibition ELISA. The results showed that the sperm motility was significantly diminished in the rats treated with different concentrations of ouabain. The number of motile sperms (grades a and b) was decreased greatly in a time- and dose-dependent manner in 10-5–10-2 mol/L ouabain groups (P<0.01), while no obvious change in sperm motility was observed in 10-7–10-6mol/L groups even for 4-h incubation (P>0.05). Furthermore, the EO level was significantly increased in asthenozoospermia patients as compared with that in males with normal fertility (25.27±1.71 μg/L in mild asthenozoospermia patients, 26.52±1.82 μg/L in severe asthenozoospermia patients, 19.31±1.45 μg/L in normal fertility men) (P<0.01). In conclusion, rat asthenozoospermia was successfully established by intraperitoneal injection of ouabain, and 10-5 mol/L ouabain was sufficient enough to inhibit sperm motility in vitro. Moreover, EO, a normal constituent of seminal plasma, was highly expressed in asthenozoospermia males as compared with normal fertility ones.

Key words

ouabain asthenozoospermia motility Na+/K+ ATPase α4 isoform 


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  1. 1.
    Thundathil JC, Anzar M, Buhr MM. Na+/K+ATPase as a signaling molecule during bovine sperm capacitation. Biol Reprod, 2006,75(3):308–317PubMedCrossRefGoogle Scholar
  2. 2.
    Schoner W, Scheiner-Bobis G. Endogenous cardiac glycosides: Hormones using the sodium pump as signal transducer. Semin Nephrol, 2005,25(5):343–351PubMedCrossRefGoogle Scholar
  3. 3.
    Dvela M, Rosen H, Ben-Ami HC, et al. Endogenous ouabain regulates cell viability. Am J Physiol Cell Physiol, 2012,302(2):C442–C452PubMedCrossRefGoogle Scholar
  4. 4.
    Jimenez T, Sanchez G, Wertheimer E, et al. Activity of the Na,K-ATPase alpha4 isoform is important for membrane potential, intracellular Ca2+, and pH to maintain motility in rat spermatozoa. Reproduction, 2010,139(5): 835–845PubMedCrossRefGoogle Scholar
  5. 5.
    Jimenez T, Sanchez G, Blanco G. Activity of the Na,K-ATPase alpha4 isoform is regulated during sperm capacitation to support sperm motility. J Androl, 2012, 33(5):1047–1057PubMedCrossRefGoogle Scholar
  6. 6.
    Harris DW, Clark MA, Fisher JF, et al. Development of an immunoassay for endogenous digitalislike factor. Hypertension, 1991,17(6 Pt 2):936–943PubMedCrossRefGoogle Scholar
  7. 7.
    Komiyama Y, Nishimura N, Munakata M, et al. Identification of endogenous ouabain in culture supernatant of PC12 cells. J Hypertens, 2001,19(2):229–236PubMedCrossRefGoogle Scholar
  8. 8.
    Yoshika M, Komiyama Y, Takahashi H. An ouabain-like factor is secreted from immortalized hypothalamic cells in an aldosterone-dependent manner. Neurochem Int, 2011,59(2):104–108PubMedCrossRefGoogle Scholar
  9. 9.
    Jimenez T, McDermott JP, Sanchez G, et al. Na,K-ATPase alpha4 isoform is essential for sperm fertility. Proc Natl Acad Sci USA, 2011,108(2):644–649PubMedCrossRefGoogle Scholar
  10. 10.
    Newton LD, Krishnakumar S, Menon AG, et al. Na+/K+ATPase regulates sperm capacitation through a mechanism involving kinases and redistribution of its testis-specific isoform. Mol Reprod Dev, 2010,77(2):136–148PubMedGoogle Scholar
  11. 11.
    Jimenez T, Sanchez G, McDermott JP, et al. Increased expression of the Na,K-ATPase alpha4 isoform enhances sperm motility in transgenic mice. Biol Reprod, 2011, 84(1):153–161PubMedCrossRefGoogle Scholar
  12. 12.
    Hlivko JT, Chakraborty S, Hlivko TJ, et al. The human Na,K-ATPase alpha 4 isoform is a ouabain-sensitive alpha isoform that is expressed in sperm. Mol Reprod Dev, 2006,73(1):101–115PubMedCrossRefGoogle Scholar
  13. 13.
    Laboratory manual of the WHO for the examination of human semen and sperm-cervical mucus interaction. Ann Ist Super Sanita, 2001,37:1–123Google Scholar
  14. 14.
    Wu L, Xiong C, Su P. Endogenous ouabain in hypertensive disorder complicating pregnancy. J Huazhong Univ Sci Technol [Med Sci], 2007,27(6):717–720CrossRefGoogle Scholar
  15. 15.
    Kocak-Toker N, Aktan G, Aykac-Toker G. The role of Na,K-ATPase in human sperm motility. Int J Androl, 2002,25(3):180–185PubMedCrossRefGoogle Scholar
  16. 16.
    Konrad L, Dietze R, Kirch U, et al. Cardiotonic steroids trigger non-classical testosterone signaling in Sertoli cells via the alpha4 isoform of the sodium pump. Biochim Biophys Acta, 2011,1813(12):2118–2124PubMedCrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Yi-hong Yang (杨宜红)
    • 1
  • Yan Wan (万 艳)
    • 1
  • Huan Lou (娄 欢)
    • 1
  • Ting Xue (薛 婷)
    • 1
  • Ping Su (苏 萍)
    • 1
    Email author
  1. 1.The Family Planning Research Institute, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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