Mitochondrial membrane potential (MMP) regulates sperm motility

  • Saurabh Kumar Agnihotri
  • Ankit Kumar Agrawal
  • Bilal Ahmad Hakim
  • A. L. Vishwakarma
  • T. Narender
  • Rekha Sachan
  • Monika Sachdev


Sperm motility is the major decisive factor in determining male fertility. The objective of the present study was to analyse the effect of mitochondrial membrane potential (MMP) on the temporal regulation of sperm motility. Observations were recorded in various rodent species and among differentially motile sperm fractions including swim up and leftover layer of human semen sample using JC-1 stain (a marker of the MMP) through FACS. Swim-up sperms having highest motility showed significantly higher MMP as compared to leftover sperms, which had the least motility. Interestingly, infertile patients with compromised motility showed low MMP as compared to the healthy individuals. Further, as per the time lapse, sperm motility goes down, at the same time, it was observed that MMP also decreases in human as well as in rodent sperms. Treatment of known spermicides on human sperms reduced their motility drastically which in turn also reduced its MMP significantly. Treatment of human sperms with oxidative uncoupler also impeded their motility by reducing MMP, indicating a definitive role on MMP on sperm motility and fertility. Based on the results of the study, MMP can be considered as a potential regulator and indicator of sperm motility and hence could be directly related to male fertility.


Mitochondrial membrane potential Spermatozoa Sperm motility Infertility 



This research work was financially supported by PROGRAM, Council of Scientific and Industrial Research (CSIR), New Delhi, Government of India. We thank CSIR—Central Drug Research Institute, Lucknow as well as the central FACS facility of the institute.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. Barratt CL, Tomlinson MJ, Cooke ID (1993) Prognostic significance of computerized motility analysis for in vivo fertility. Fertil Steril 60:520–525CrossRefPubMedGoogle Scholar
  2. Barroso G, Taylor S, Morshedi M, Manzur F, Gavino F, Oehninger S (2006) Mitochondrial membrane potential integrity and plasma membrane translocation of phosphatidylserine as early apoptotic markers: a comparison of two different sperm subpopulations. Fertil Steril 85:149–154CrossRefPubMedGoogle Scholar
  3. Brugh VM III, Lipshultz LI (2004) Male factor infertility: evaluation and management. Med Clin North Am 88:367–385CrossRefPubMedGoogle Scholar
  4. Cummins JM, Woodall PF (1985) On mammalian sperm dimensions. J Reprod Fertil 75:153–175CrossRefPubMedGoogle Scholar
  5. Donnelly ET, Lewis SE, McNally JA, Thompson W (1998) In vitro fertilization and pregnancy rates: the influence of sperm motility and morphology on IVF outcome. Fertil Steril 70:305–314CrossRefPubMedGoogle Scholar
  6. Folgero T, Bertheussen K, Lindal S, Torbergsen T, Oian P (1993) Mitochondrial disease and reduced sperm motility. Hum Reprod 8:1863–1868PubMedGoogle Scholar
  7. Gallon F, Marchetti C, Jouy N, Marchetti P (2006) The functionality of mitochondria differentiates human spermatozoa with high and low fertilizing capability. Fertil Steril 86:1526–1530CrossRefPubMedGoogle Scholar
  8. Jodar M, Kalko S, Castillo J, Ballesca JL, Oliva R (2012) Differential RNAs in the sperm cells of asthenozoospermic patients. Hum Reprod 27:1431–1438CrossRefPubMedGoogle Scholar
  9. Kasai T, Ogawa K, Mizuno K, Nagai S, Uchida Y, Ohta S, Fujie M, Suzuki K, Hirata S, Hoshi K (2002) Relationship between sperm mitochondrial membrane potential, sperm motility, and fertility potential. Asian J Androl 4:97–103PubMedGoogle Scholar
  10. Krause W (1995) Computer-assisted semen analysis systems: comparison with routine evaluation and prognostic value in male fertility and assisted reproduction. Hum Reprod 10(Suppl 1):60–66CrossRefPubMedGoogle Scholar
  11. Marchetti C, Jouy N, Leroy-Martin B, Defossez A, Formstecher P, Marchetti P (2004) Comparison of four fluorochromes for the detection of the inner mitochondrial membrane potential in human spermatozoa and their correlation with sperm motility. Hum Reprod 19:2267–2276CrossRefPubMedGoogle Scholar
  12. Marchetti C, Obert G, Deffosez A, Formstecher P, Marchetti P (2002) Study of mitochondrial membrane potential, reactive oxygen species, DNA fragmentation and cell viability by flow cytometry in human sperm. Hum Reprod 17:1257–1265CrossRefPubMedGoogle Scholar
  13. Ortega C, Verheyen G, Raick D, Camus M, Devroey P, Tournaye H (2011) Absolute asthenozoospermia and ICSI: what are the options? Hum Reprod Update 17:684–692CrossRefPubMedGoogle Scholar
  14. Piasecka M, Kawiak J (2003) Sperm mitochondria of patients with normal sperm motility and with asthenozoospermia: morphological and functional study. Folia Histochem Cytobiol 41:125–139PubMedGoogle Scholar
  15. Piasecka M, Laszczynska M, Gaczarzewicz D (2003) Morphological and functional evaluation of spermatozoa from patients with asthenoteratozoospermia. Folia Morphol (Warsz) 62:479–481Google Scholar
  16. Poongothai J, Gopenath TS, Manonayaki S (2009) Genetics of human male infertility. Singap Med J 50:336–347Google Scholar
  17. Srivastav A, Chandra A, Singh M, Jamal F, Rastogi P, Rajendran SM, Bansode FW, Lakshmi V (2010) Inhibition of hyaluronidase activity of human and rat spermatozoa in vitro and antispermatogenic activity in rats in vivo by Terminalia chebula, a flavonoid rich plant. Reprod Toxicol 29(2):214–224CrossRefPubMedGoogle Scholar
  18. Wang J, Wang J, Zhang HR, Shi HJ, Ma D, Zhao HX, Lin B, Li RS (2009) Proteomic analysis of seminal plasma from asthenozoospermia patients reveals proteins that affect oxidative stress responses and semen quality. Asian J Androl 11:484–491CrossRefPubMedPubMedCentralGoogle Scholar
  19. Wang X, Sharma RK, Gupta A, George V, Thomas AJ, Falcone T, Agarwal A (2003a) Alterations in mitochondria membrane potential and oxidative stress in infertile men: a prospective observational study. Fertil Steril 80(Suppl 2):844–850CrossRefPubMedGoogle Scholar
  20. Wang X, Sharma RK, Sikka SC, Thomas AJ Jr, Falcone T, Agarwal A (2003b) Oxidative stress is associated with increased apoptosis leading to spermatozoa DNA damage in patients with male factor infertility. Fertil Steril 80:531–535CrossRefPubMedGoogle Scholar
  21. World Health Organization (1999) WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. Cambridge university pressGoogle Scholar
  22. World Health Organization. Infertility: a tabulation of available data on prevalence of primary and secondary infertility. Geneva, Switzerland: WHO Programme on Maternal and Child Health and Family Planning; 1991:1–72Google Scholar

Copyright information

© The Society for In Vitro Biology 2016

Authors and Affiliations

  • Saurabh Kumar Agnihotri
    • 1
  • Ankit Kumar Agrawal
    • 1
  • Bilal Ahmad Hakim
    • 1
  • A. L. Vishwakarma
    • 2
  • T. Narender
    • 3
  • Rekha Sachan
    • 4
  • Monika Sachdev
    • 1
  1. 1.Endocrinology DivisionCSIR- Central Drug Research InstituteLucknowIndia
  2. 2.Sophisticated Analytical Instrument FacilityCSIR- Central Drug Research InstituteLucknowIndia
  3. 3.Medicinal and Process Chemistry DivisionCSIR- Central Drug Research InstituteLucknowIndia
  4. 4.Department of Obstetrics and GynaecologyKing Georges’ Medical UniversityLucknowIndia

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