Lactate dehydrogenase C4 (LDH-C4) is essential for the sperm count and motility: A case-control study
Keywords:azoospermia, Km, Lactate dehydrogenase C4 activity, oligospermia, Vmax
Background: The lactate dehydrogenase C4 (LDH-C4) isoenzyme is an important enzyme involved in metabolic processes that are needed for spermatogenesis and sperm motility.
Objectives: This study aims to assess the activity and kinetic parameters (maximum velocity, Vmax and Michaelis constant, Km) of LDH-C4 in fertile and infertile (azoospermia and oligospermia) men in Baghdad City, Iraq.
Methods: A total of 120 participants (80 infertile and 40 healthy fertile men) were included in the current study. The patients were sub-grouped into: 40 infertile men with oligospermia, and 40 infertile men with azoospermia. The oligospermia patients were further subdivided into subgroups based on sperm count and motility. Semen samples were obtained by masturbation after 3-5 days abstain for seminal fluid analysis. The microscopic test included the assessment of the count, motility and morphology of the sperms. In addition, the coulometric assay was used for measuring the activity and kinetic parameters of LDH-C4 enzyme.
Results: The activity of LDH-C4 is significantly higher in fertile men when compared with infertile subjects (fertile: 403.13±189.90, oligospermia: 110.01±58.13, azoospermia: 39.06±28.15; p≤0.01). Statistically significant differences in LDH-C4 activity were also noted among patients with oligospermia based on sperms count and motility. Based on sperms’ count in patients with oligospermia, a significantly higher LDH-C4 activity (p≤0.01) was noted in those with higher sperm count (10-15 million/ml) when compared to others who have lesser count. Significant elevation in enzyme activity (p≤0.01) was also observed in oligospermia patients with higher percentages of motile sperms when compared with others who have fewer percentages of motile sperms. Moreover, the highest Vmax value (0.483 mmol/L.min) and the lowest Km value (0.39 mmol/L) were recorded in fertile men. While, the lowest Vmax value (0.174 mmol/L.min) and the lowest Km value (0.75 mmol/L) were detected in azoospermia patients.
Conclusions: Our results suggest that LDH-C4 is essential for the count and motility of sperm and may be considered as a therapeutic approach for infertility.
A C Williams and Wcl Ford. “The role of glucose in supporting motility and capacitation in human spermatozoa”. J Androl 22(4) (2001), pp. 680–695. DOI: 10.1002/j.1939-4640.2001.tb02229.x.
A Forkasiewicz et al. “The usefulness of lactate dehydrogenase measurements in current oncological practice”. Cell Mol Biol Lett 25 (2020), pp. 35–35. DOI: 10.1186/s11658-020-00228-7. DOI: https://doi.org/10.1186/s11658-020-00228-7
A J Armstrong, D J George, and S Halabi. “Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin”. J Clin Oncol 30(27) (2012), pp. 3402–3407. DOI: 10.1200/JCO.2011.40.9631. DOI: https://doi.org/10.1200/JCO.2011.40.9631
A Rogers and Y Gibon. “Enzyme Kinetics: Theory and Practice”. In: Springer, 2009, pp. 71–103. DOI: 10.1007/978-0-387-78745-9_4. DOI: https://doi.org/10.1007/978-0-387-78745-9_4
A Talaiezadeh et al. “Kinetic characterization of lactate dehydrogenase in normal and malignant human breast tissues”. Cancer Cell Int 15(1) (2015), pp. 19–19. DOI: 10.1186/s12935-015-0171-7. DOI: https://doi.org/10.1186/s12935-015-0171-7
Al-Bajari Sa, Al-Lehebe Ni, and S A Hazzaa. “Purification of lactate dehydrogenase-C4 from seminal plasma of male infertility”. Basrah J Vet Res 17(3) (2018), pp. 726–737.
C Mukai and M Okuno. “Glycolysis plays a major role for adenosine triphosphate supplementation in mouse sperm flagellar movement”. Biol Reprod 71(2) (2004), pp. 540–547. DOI: 10.1095/biolreprod.103.026054. DOI: https://doi.org/10.1095/biolreprod.103.026054
D Heinová, Z Kostecká, and T Csank. “Separation of turkey lactate dehydrogenase isoenzymes using isoelectric focusing technique”. Electrophoresis 37(2) (2016), pp. 335–338. DOI: 10.1002/elps.201500407. DOI: https://doi.org/10.1002/elps.201500407
E Ruiz-Pesini et al. “The role of the mitochondrion in sperm function: is there a place for oxidative phosphorylation or is this a purely glycolytic process?” Curr Top Dev Biol 77 (2007), pp. 3–19. DOI: 10.1016/S0070-2153(06)77001-6. DOI: https://doi.org/10.1016/S0070-2153(06)77001-6
Erwin Goldberg and Rcd. “Inhibiting Human Lactate Dehydrogenase-C for Male Fertility Control; Initial Hits”. J Pharm Drug Deliv Res(02) (2014), pp. 3–3. DOI: 10.4172/2325-9604.1000125. DOI: https://doi.org/10.4172/2325-9604.1000125
F Odet et al. “Lactate dehydrogenase C and energy metabolism in mouse sperm”. Biol Reprod 85(3) (2011), pp. 556–564. DOI: 10.1095/biolreprod.111.091546. DOI: https://doi.org/10.1095/biolreprod.111.091546
F Odet, C Duan, and W D Willis. “Expression of the gene for mouse lactate dehydrogenase C (Ldhc) is required for male fertility”. Biol Reprod 79(1) (2008), pp. 26–34. DOI: 10.1095/biolreprod.108.068353. DOI: https://doi.org/10.1095/biolreprod.108.068353
I Jialal and L J Sokoll. “Clinical utility of lactate dehydrogenase: a historical perspective”. Am J Clin Pathol 143(2) (2015), pp. 158–159. DOI: 10.1309/AJCTP0FC8QFYDFA. DOI: https://doi.org/10.1309/AJCTP0FC8QFYDFA
K Vaidyanathan. Textbook of Biochemistry for Medical Students. Ed. by and others. 2016. DOI: doi:10.5005/jp/books/13014. DOI: https://doi.org/10.5005/jp/books/13014
M Gavella and P Cvitkovi´c. “Semen LDH-X deficiency and male infertility”. Arch Androl 15(2-3) (1985), pp. 173–176. DOI: 10.3109/01485018508986907. DOI: https://doi.org/10.3109/01485018508986907
M Hashemi et al. “Evaluation of LDH activity and its relationship with fructose levels in seminal plasma of normospermic and asthenospermic males”. Med Lab J 10(4) (2016), pp. 18–23. DOI: 10.18869/acadpub.mlj.10.4.18. DOI: https://doi.org/10.18869/acadpub.mlj.10.4.18
M J Mccabe, R E Bancalari, and M T Dattani. “Diagnosis and evaluation of hypogonadism”. Pediatr Endocrinol Rev 11(2) (2014), pp. 214–229.
M V Sawane et al. “Seminal LDH-C4 isoenzyme and sperm mitochondrial activity: a study in male partners of infertile couples”. Indian J Med Sci 56(11) (2002), pp. 560–566.
N M Gerez De Burgos et al. “Correlation of lactate dehydrogenase isoenzyme C4 activity with the count and motility of human spermatozoa”. J Reprod Fertil 55(1) (1979), pp. 107–111. DOI: 10.1530/jrf.0.0550107. DOI: https://doi.org/10.1530/jrf.0.0550107
Nhpm Jutte et al. “Exogenous lactate is essential for metabolic activities in isolated rat spermatocytes and spermatids”. J Reprod Fertil (1981). DOI: 10.1530/jrf.0.0620399. DOI: https://doi.org/10.1530/jrf.0.0620399
Noguera Velasco et al. “Lactic dehydrogenase-C4 activity in seminal plasma and male infertility”. Fertil Steril 60(2) (1993), pp. 56107–56107. DOI: 10.1016/s0015-0282(16)56107-x. DOI: https://doi.org/10.1016/S0015-0282(16)56107-X
Omar A. El Seoud, Wilhelm J. Baader, and Erick L. Bastos. “Practical Chemical Kinetics in Solution”. In: Encyclopedia of Physical Organic Chemistry. Ed. by Zerong Wang et al. John Wiley & Sons, Inc., 2016, pp. 1–68. DOI: 10.1002/9781118468586.epoc1012. DOI: https://doi.org/10.1002/9781118468586.epoc1012
P C Champe, R A Harvey, and D R Ferrier. Biochemistry. Ed. by and others. 5th ed. Lippincott Williams & Wilkins, 2010.
P Piomboni et al. “The role of mitochondria in energy production for human sperm motility”. Int J Androl 35(2) (2012), pp. 109–124. DOI: https://doi.org/10.1111/j.1365-2605.2011.01218.x
P Tang et al. “A mechanistic kinetic description of lactate dehydrogenase elucidating cancer diagnosis and inhibitor evaluation”. J Enzyme Inhib Med Chem 32(1) (2017), pp. 564–571. DOI: 10.1080/14756366.2016.1275606. DOI: https://doi.org/10.1080/14756366.2016.1275606
U Satyanarayana and U Chakrapani. Essentials of Biochemistry. Ed. by and others. 2008.
Y Wang et al. “Testis-Specific Lactate Dehydrogenase (LDH-C4) in Skeletal Muscle Enhances a Pika’s Sprint-Running Capacity in Hypoxic Environment”. Int J Environ Res Public Health 12(8) (2015), pp. 9218–9236. DOI: 10.3390/ijerph120809218. DOI: https://doi.org/10.3390/ijerph120809218
How to Cite
Copyright (c) 2021 Baraa A. Saeed, Rayah S. Baban, Usama S. Al-Nasiri
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The authors retain the copyright of their manuscript by submitting the work to this journal, and all open access articles are distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC-BY-NC 4.0), which permits use for any non-commercial purpose, distribution, and reproduction in any medium, provided that the original work is properly cited.