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Sodium-Hydrogen-Exchanger expression in human sperm and its relationship with semen parameters

  • Zhe Zhang
  • Yuzhuo Yang
  • Han Wu
  • Hongliang Zhang
  • Haitao Zhang
  • Jiaming Mao
  • Defeng Liu
  • Lianming Zhao
  • Haocheng Lin
  • Wenhao Tang
  • Kai Hong
  • Hui JiangEmail author
Gamete Biology

Abstract

Purpose

Sperm-specific sodium-hydrogen exchanger (sNHE) is essential to maintain sperm normal function in mice; however, its role in human sperm has not been clarified to date. The aim of this study is to investigate the expression pattern of sNHE in human spermatozoa and its relationship with sperm functional parameters.

Method

Semen samples from 68 asthenozoospermic and 61 normozoospermic men were analyzed for sperm concentration, motility, and acrosome reaction, and high motile spermatozoa were collected by swim-up method. The expression of sNHE in spermatozoa was detected by Western blot and immunofluorescence staining. The relationship between sNHE expression and sperm parameters was assessed.

Results

We identified sNHE is mainly localized to the principal piece of the human sperm tail. The expression of sNHE was positively correlated with sperm concentration, total number, and progressive motility. Moreover, sNHE expression was upregulated in swim-up sperm and associated with most of sperm motility parameters including straight line velocity and curvilinear velocity. Our results also showed that sNHE expression is decreased in sperm from patients with asthenozoospermia compared with that from normal controls. However, no correlation was found between sNHE expression and acrosome reaction in spermatozoa.

Conclusions

The expression pattern of sNHE suggested that this protein may be involved in the regulation of sperm motility, and aberration of its expression in sperm may contribute to the pathogenesis of asthenozoospermia.

Keywords

Sodium-hydrogen exchanger Human sperm Motility parameters Asthenozoospermia Male infertility 

Notes

Acknowledgments

This work was supported by Peking University 985 Clinical Hospital Cooperation Program to Hui Jiang.

Compliance with ethical standards

The study was approved by the Ethical Committee and conducted according to the Helsinki Declaration. Every subject was fully informed of the purpose of the study and provided informed consent before the research.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Skakkebaek NE, Jorgensen N, Main KM, Rajpert-De Meyts E, Leffers H, Andersson AM, et al. Is human fecundity declining? Int J Androl. 2006;29(1):2–11. doi: 10.1111/j.1365-2605.2005.00573.x.CrossRefPubMedGoogle Scholar
  2. 2.
    Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril. 2015;103(3):e18–25. doi: 10.1016/j.fertnstert.2014.12.103.
  3. 3.
    Yoshida M, Kawano N, Yoshida K. Control of sperm motility and fertility: diverse factors and common mechanisms. Cellular and molecular life sciences: CMLS. 2008;65(21):3446–57. doi: 10.1007/s00018-008-8230-z.CrossRefPubMedGoogle Scholar
  4. 4.
    Bajpai M, Doncel GF. Involvement of tyrosine kinase and cAMP-dependent kinase cross-talk in the regulation of human sperm motility. Reproduction (Cambridge, England). 2003;126(2):183–95.CrossRefGoogle Scholar
  5. 5.
    Singh AP, Rajender S. CatSper channel, sperm function and male fertility. Reprod BioMed Online. 2015;30(1):28–38. doi: 10.1016/j.rbmo.2014.09.014.CrossRefPubMedGoogle Scholar
  6. 6.
    Skalhegg BS, Huang Y, Su T, Idzerda RL, McKnight GS, Burton KA. Mutation of the Calpha subunit of PKA leads to growth retardation and sperm dysfunction. Molecular endocrinology (Baltimore, Md). 2002;16(3):630–9. doi: 10.1210/mend.16.3.0793.Google Scholar
  7. 7.
    Liu SW, Li Y, Zou LL, Guan YT, Peng S, Zheng LX, et al. Chloride channels are involved in sperm motility and are downregulated in spermatozoa from patients with asthenozoospermia. Asian journal of andrology. 2016; doi: 10.4103/1008-682x.181816.Google Scholar
  8. 8.
    Liu B, Wang P, Wang Z, Jia Y, Niu X, Wang W, et al. Analysis and difference of voltage-dependent anion channel mRNA in ejaculated spermatozoa from normozoospermic fertile donors and infertile patients with idiopathic asthenozoospermia. J Assist Reprod Genet. 2010a;27(12):719–24. doi: 10.1007/s10815-010-9466-8.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Donowitz M, Ming Tse C, Fuster D. SLC9/NHE gene family, a plasma membrane and organellar family of Na+/H+ exchangers. Mol Asp Med. 2013;34(2–3):236–51. doi: 10.1016/j.mam.2012.05.001.CrossRefGoogle Scholar
  10. 10.
    Fuster DG, Alexander RT. Traditional and emerging roles for the SLC9 Na+/H+ exchangers. Pflugers Archiv: European journal of physiology. 2014;466(1):61–76. doi: 10.1007/s00424-013-1408-8.CrossRefPubMedGoogle Scholar
  11. 11.
    Xu H, Chen H, Li J, Zhao Y, Ghishan FK. Disruption of NHE8 expression impairs Leydig cell function in the testes. American journal of physiology Cell physiology. 2015;308(4):C330–8. doi: 10.1152/ajpcell.00289.2014.CrossRefPubMedGoogle Scholar
  12. 12.
    Woo AL, James PF, Lingrel JB. Roles of the Na, K-ATPase alpha 4 isoform and the Na+/H+ exchanger in sperm motility. Mol Reprod Dev. 2002;62(3):348–56. doi: 10.1002/mrd.90002.CrossRefPubMedGoogle Scholar
  13. 13.
    Wang D, King SM, Quill TA, Doolittle LK, Garbers DL. A new sperm-specific Na+/H+ exchanger required for sperm motility and fertility. Nat Cell Biol. 2003;5(12):1117–22. doi: 10.1038/ncb1072.CrossRefPubMedGoogle Scholar
  14. 14.
    Bell SM, Schreiner CM, Schultheis PJ, Miller ML, Evans RL, Vorhees CV, et al. Targeted disruption of the murine Nhe1 locus induces ataxia, growth retardation, and seizures. Am J Phys. 1999;276(4 Pt 1):C788–95.Google Scholar
  15. 15.
    Liu T, Huang JC, Zuo WL, Lu CL, Chen M, Zhang XS, et al. A novel testis-specific Na+/H+ exchanger is involved in sperm motility and fertility. Frontiers in bioscience (Elite edition). 2010b;2:566–81.CrossRefGoogle Scholar
  16. 16.
    Mortimer ST, Swan MA, Mortimer D. Effect of seminal plasma on capacitation and hyperactivation in human spermatozoa. Human reproduction (Oxford, England). 1998;13(8):2139–46.CrossRefGoogle Scholar
  17. 17.
    Hamamah S, Gatti JL. Role of the ionic environment and internal pH on sperm activity. Human reproduction (Oxford, England). 1998;13(Suppl 4):20–30.CrossRefGoogle Scholar
  18. 18.
    Darszon A, Trevino CL, Wood C, Galindo B, Rodriguez-Miranda E, Acevedo JJ, et al. Ion channels in sperm motility and capacitation. Society of Reproduction and Fertility supplement. 2007;65:229–44.PubMedGoogle Scholar
  19. 19.
    Wang D, Hu J, Bobulescu IA, Quill TA, McLeroy P, Moe OW, et al. A sperm-specific Na+/H+ exchanger (sNHE) is critical for expression and in vivo bicarbonate regulation of the soluble adenylyl cyclase (sAC). Proc Natl Acad Sci U S A. 2007;104(22):9325–30. doi: 10.1073/pnas.0611296104.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Tamburrino L, Marchiani S, Vicini E, Muciaccia B, Cambi M, Pellegrini S, et al. Quantification of CatSper1 expression in human spermatozoa and relation to functional parameters. Human reproduction (Oxford, England). 2015;30(7):1532–44. doi: 10.1093/humrep/dev 103. CrossRefGoogle Scholar
  21. 21.
    Soda T, Miyagawa Y, Ueda N, Takezawa K, Okuda H, Fukuhara S, et al. Systematic characterization of human testis-specific actin capping protein β3 as a possible biomarker for male infertility. Hum Reprod (Oxford, England). 2017 Jan 18; doi: 10.1093/humrep/dew 353.Google Scholar
  22. 22.
    Shi Y, Yuan H, Kim D, Chanana V, Baba A, Matsuda T, et al. Stimulation of Na+/H+ exchanger isoform 1 promotes microglial migration. PLoS One. 2013;8(8):e74201. doi: 10.1371/journal.pone.0074201.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Huetsch JC, Jiang H, Larrain C, Shimoda LA. The Na+/H+ exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension. Physiological reports. 2016;4:5. doi: 10.14814/phy2.12729.CrossRefGoogle Scholar
  24. 24.
    Van den Bergh M, Emiliani S, Biramane J, Vannin AS, Englert Y. A first prospective study of the individual straight line velocity of the spermatozoon and its influences on the fertilization rate after intracytoplasmic sperm injection. Human reproduction (Oxford, England). 1998;13(11):3103–7.CrossRefGoogle Scholar
  25. 25.
    Florman HM, Jungnickel MK, Sutton KA. Shedding light on sperm pHertility. Cell. 2010;140(3):310–2. doi: 10.1016/j.cell.2010.01.035.CrossRefPubMedGoogle Scholar
  26. 26.
    Nishigaki T, Jose O, Gonzalez-Cota AL, Romero F, Trevino CL, Darszon A. Intracellular pH in sperm physiology. Biochem Biophys Res Commun. 2014;450(3):1149–58. doi: 10.1016/j.bbrc.2014.05.100.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Suarez SS. Control of hyperactivation in sperm. Hum Reprod Update. 2008;14(6):647–57. doi: 10.1093/humupd/dmn029.CrossRefPubMedGoogle Scholar
  28. 28.
    Wiser A, Sachar S, Ghetler Y, Shulman A, Breitbart H. Assessment of sperm hyperactivated motility and acrosome reaction can discriminate the use of spermatozoa for conventional in vitro fertilisation or intracytoplasmic sperm injection: preliminary results. Andrologia. 2014;46(3):313–5. doi: 10.1111/and.12068.CrossRefPubMedGoogle Scholar
  29. 29.
    Stival C, Puga Molina Ldel C, Paudel B, Buffone MG, Visconti PE, Krapf D. Sperm capacitation and acrosome reaction in mammalian sperm. Adv Anat Embryol Cell Biol. 2016;220:93–106. doi: 10.1007/978-3-319-30567-7_5.CrossRefPubMedGoogle Scholar
  30. 30.
    Garcia MA, Meizel S. Regulation of intracellular pH in capacitated human spermatozoa by a Na+/H+ exchanger. Mol Reprod Dev. 1999;52(2):189–95. doi: 10.1002/(sici)1098-2795(199902)52:2<189::aid-mrd10>3.0.co;2-d.CrossRefPubMedGoogle Scholar
  31. 31.
    Tomlinson M, Lewis S, Morroll D. Sperm quality and its relationship to natural and assisted conception: British fertility society guidelines for practice. Human fertility (Cambridge, England). 2013;16(3):175–93. doi: 10.3109/14647273.2013.807522.CrossRefGoogle Scholar
  32. 32.
    Verheyen G, Tournaye H, Staessen C, De Vos A, Vandervorst M, Van Steirteghem A. Controlled comparison of conventional in-vitro fertilization and intracytoplasmic sperm injection in patients with asthenozoospermia. Human reproduction (Oxford, England). 1999;14(9):2313–9.CrossRefGoogle Scholar
  33. 33.
    Ben-Chetrit A, Senoz S, Greenblatt EM, Casper RF. In vitro fertilization outcome in the presence of severe male factor infertility. Fertil Steril. 1995;63(5):1032–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Liu T, Huang JC, Lu CL, Yang JL, Hu ZY, Gao F, et al. Immunization with a DNA vaccine of testis-specific sodium-hydrogen exchanger by oral feeding or nasal instillation reduces fertility in female mice. Fertil Steril. 2010c;93(5):1556–66. doi: 10.1016/j.fertnstert.2009.03.056.CrossRefPubMedGoogle Scholar
  35. 35.
    Peralta-Arias RD, Vívenes CY, Camejo MI, Piñero S, Proverbio T, Martínez E, et al. ATPases, ion exchangers and human sperm motility. Reproduction. 2015;149(5):475–84. doi: 10.1530/REP-14-0471.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Zhe Zhang
    • 1
  • Yuzhuo Yang
    • 1
  • Han Wu
    • 1
  • Hongliang Zhang
    • 2
  • Haitao Zhang
    • 1
  • Jiaming Mao
    • 3
  • Defeng Liu
    • 3
  • Lianming Zhao
    • 1
  • Haocheng Lin
    • 1
  • Wenhao Tang
    • 1
  • Kai Hong
    • 1
  • Hui Jiang
    • 1
    Email author
  1. 1.Department of UrologyPeking University Third HospitalBeijingChina
  2. 2.Department of Human Sperm BankPeking University Third HospitalBeijingChina
  3. 3.Department of Reproductive Medicine CenterPeking University Third HospitalBeijingChina

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