A sperm-specific proteome-scale metabolic network model identifies non-glycolytic genes for energy deficiency in asthenozoospermia

References

• Agarwal, A. and Said, T.M. (2004) Carnitines and male infertility. Reprod Biomed Online 8: 376–384.
   PubMed Web of Science ®Google Scholar
• Agarwal, A., Sharma, R., Samanta, L., Durairajanayagam, D. and Sabanegh, E. (2016) Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility. Asian J Androl 18: 282–291.
   PubMed Web of Science ®Google Scholar
• Amaral, A. and Ramalho‐Santos, J. (2010) Assessment of mitochondrial potential: implications for the correct monitoring of human sperm function. Int J Androl 33: e180–e186.
   Google Scholar
• Amaral, A., Castillo, J., Ramalho-Santos, J. and Oliva, R. (2013a) The combined human sperm proteome: cellular pathways and implications for basic and clinical science. Human Reprod Update 20: 40–62.
   PubMed Web of Science ®Google Scholar
• Amaral, A., Lourenço, B., Marques, M. and Ramalho-Santos, J. (2013b) Mitochondria functionality and sperm quality. Reproduction 146: R163–R174.
   PubMed Web of Science ®Google Scholar
• Amaral, A., Castillo, J., Estanyol, J.M., Ballescà, J.L., Ramalho-Santos, J. and Oliva, R. (2013c) Human sperm tail proteome suggests new endogenous metabolic pathways. Mol Cell Proteomics 12: 330–342.
   PubMed Web of Science ®Google Scholar
• Amaral, A., Paiva, C., Attardo Parrinello, C., Estanyol, J.M., Ballescà, J.L., Ramalho-Santos, J., et al. (2014) Identification of proteins involved in human sperm motility using high-throughput differential proteomics. J Proteome Res 13: 5670–5684.
   PubMed Web of Science ®Google Scholar
• Ashrafzadeh, A., Karsani, S.A. and Nathan, S. (2013) Mammalian sperm fertility related proteins. Int J Med Sci 10: 1649.
   PubMed Web of Science ®Google Scholar
• Balercia, G., Buldreghini, E., Vignini, A., Tiano, L., Paggi, F., Amoroso, S., et al. (2009) Coenzyme Q 10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. Fertil Steril 91: 1785–1792.
   PubMed Web of Science ®Google Scholar
• Bansal, S.K., Gupta, N., Sankhwar, S.N. and Rajender, S. (2015) Differential Genes Expression between Fertile and Infertile Spermatozoa Revealed by Transcriptome Analysis. PloS One 10: e0127007.
   PubMed Web of Science ®Google Scholar
• Bartellini, M., Canale, D., Izzo, P., Giorgi, P., Meschini, P. and Mechini-Fabris, G. (1986) L-carnitine and acetylcarnitine in human sperm with normal and reduced motility. Acta Europ Fertil 18: 29–31.
   Google Scholar
• Bordbar, A., Monk, J.M., King, Z.A. and Palsson, B.O. (2014) Constraint-based models predict metabolic and associated cellular functions. Nature Rev Genet 15: 107–120.
   PubMed Web of Science ®Google Scholar
• Brown, G.C. (1995) Nitric oxide regulates mitochondrial respiration and cell functions by inhibiting cytochrome oxidase. FEBS Lett 369: 136–139.
   PubMed Web of Science ®Google Scholar
• Cappello, A.R., Guido, C., Santoro, A., Santoro, M., Capobianco, L., Montanaro, D., et al. (2012) The mitochondrial citrate carrier (CIC) is present and regulates insulin secretion by human male gamete. Endocrinology 153: 1743–1754.
   PubMed Web of Science ®Google Scholar
• Chan, C.-C., Shui, H.-A., Wu, C.-H., Wang, C.-Y., Sun, G.-H., Chen, H.-M., et al. (2009) Motility and protein phosphorylation in healthy and asthenozoospermic sperm. J Proteome Res 8: 5382–5386.
   PubMed Web of Science ®Google Scholar
• Chi, A. and Kemp, R.G. (2000) The primordial high energy compound: ATP or inorganic pyrophosphate? J Biol Chem 275: 35677–35679.
   Google Scholar
• Costa, M., Canale, D., Filicori, M., D’lddio, S. and Lenzi, A. (1994) L‐carnitine in idiopathic asthenozoospermia: a multicenter study. Andrologia 26: 155–159.
   PubMed Web of Science ®Google Scholar
• Dada, R., Mahfouz, R. Z., Kumar, R., Venkatesh, S., Shamsi, M. B., Agarwal, A., et al. (2011) A comprehensive work up for an asthenozoospermic man with repeated intracytoplasmic sperm injection (ICSI) failure. Andrologia 43: 368–372.
   PubMed Web of Science ®Google Scholar
• De Rosa, M., Zarrilli, S., Paesano, L., Carbone, U., Boggia, B., Petretta, M., et al. (2003) Traffic pollutants affect fertility in men. Human Reprod 18: 1055–1061.
   PubMed Web of Science ®Google Scholar
• Dirami, T., Rode, B., Jollivet, M., Da Silva, N., Escalier, D., Gaitch, N., et al. (2013) Missense mutations in SLC26A8, encoding a sperm-specific activator of CFTR, are associated with human asthenozoospermia. Am J Human Genet 92: 760–766.
   PubMed Web of Science ®Google Scholar
• Dreanno, C., Cosson, J., Suquet, M., Seguin, F., Dorange, G. and Billard, R. (1999) Nucleotide content, oxydative phosphorylation, morphology, and fertilizing capacity. Mol Reprod Dev 53: 230–243.
   PubMed Web of Science ®Google Scholar
• Du, Y., Li, M., Chen, J., Duan, Y., Wang, X., Qiu, Y., et al. (2015) Promoter targeted bisulfite sequencing reveals DNA methylation profiles associated with low sperm motility in asthenozoospermia. Human Reprod 31: 24–33.
   PubMed Web of Science ®Google Scholar
• Duarte, N.C., Becker, S.A., Jamshidi, N., Thiele, I., Mo, M.L., Vo, T.D., et al. (2007) Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc Natl Acad Sci 104: 1777–1782.
   PubMed Web of Science ®Google Scholar
• Eslamian, G., Amirjannati, N., Rashidkhani, B., Sadeghi, M.-R., Baghestani, A.-R. and Hekmatdoost, A. (2015) Dietary fatty acid intakes and asthenozoospermia: a case-control study. Fertil Steril 103: 190–198.
   PubMed Web of Science ®Google Scholar
• Ford, W. (2006) Glycolysis and sperm motility: does a spoonful of sugar help the flagellum go round? Human Reprod Update 12: 269–274.
   Google Scholar
• Ford, W. and Harrison, A. (1981) The role of oxidative phosphorylation in the generation of ATP in human spermatozoa. J Reprod Fertil 63: 271–278.
   PubMedGoogle Scholar
• Forgac, M. (2007) Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology. Nature Reviews Mol Cell Biol 8: 917–929.
   PubMed Web of Science ®Google Scholar
• Fouladiha, H., Marashi, S.A. and Shokrgozar, M. (2015) Reconstruction and validation of a constraint‐based metabolic network model for bone marrow‐derived mesenchymal stem cells. Cell Prolif 48: 475–485.
   PubMed Web of Science ®Google Scholar
• Frezza, C., Zheng, L., Folger, O., Rajagopalan, K.N., MacKenzie, E.D., Jerby, L., et al. (2011) Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature 477: 225–228.
   PubMed Web of Science ®Google Scholar
• Fukushima, T., Kaneoka, H., Yasuno, T., Sasaguri, Y., Tokuyasu, T., Tokoro, K., et al. (2013) Three novel mutations in the carnitine–acylcarnitine translocase (CACT) gene in patients with CACT deficiency and in healthy individuals. J Human Genet 58: 788–793.
   PubMed Web of Science ®Google Scholar
• Golan, R., Weissenberg, R. and Lewin, L. (1984) Carnitine and acetylcarnitine in motile and immotile human spermatozoa. Int J Androl 7: 484–494.
   PubMedGoogle Scholar
• Goodrich, R.J., Anton, E. and Krawetz, S.A. (2013) Isolating mRNA and small noncoding RNAs from human sperm. Methods Mol Biol 927: 385–396.
   PubMedGoogle Scholar
• Gurunath, S., Pandian, Z., Anderson, R.A. and Bhattacharya, S. (2011) Defining infertility—a systematic review of prevalence studies. Human Reprod Update 17: 575–588.
   PubMed Web of Science ®Google Scholar
• Hadi, M. and Marashi, S.-A. (2014) Reconstruction of a generic metabolic network model of cancer cells. Mol BioSystems 10: 3014–3021.
   PubMed Web of Science ®Google Scholar
• Hinton, B., Snoswell, A. and Setchell, B. (1979) The concentration of carnitine in the luminal fluid of the testis and epididymis of the rat and some other mammals. J Reprod Fertil 56: 105–111.
   PubMedGoogle Scholar
• Huang, D.W., Sherman, B.T. and Lempicki, R.A. (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols 4: 44–57.
   PubMed Web of Science ®Google Scholar
• Hwang, K., Walters, R.C. and Lipshultz, L.I. (2011) Contemporary concepts in the evaluation and management of male infertility. Nature Rev Urol 8: 86–94.
   PubMed Web of Science ®Google Scholar
• Jerby, L., Shlomi, T. and Ruppin, E. (2010) Computational reconstruction of tissue‐specific metabolic models: application to human liver metabolism. Mol Syst Biol 7: 401.
   Google Scholar
• Jodar, M., Sendler, E. and Krawetz, S.A. (2016) The protein and transcript profiles of human semen. Cell Tissue Res 363: 85–96.
   PubMed Web of Science ®Google Scholar
• John, J.C., Jokhi, R.P. and Barratt, C.L. (2005) The impact of mitochondrial genetics on male infertility. Int J Androl 28: 65–73.
   PubMedGoogle Scholar
• Johnson, G., Sendler, E., Lalancette, C., Hauser, R., Diamond, M.P. and Krawetz, S. (2011) Cleavage of rRNA ensures translational cessation in sperm at fertilization. Mol Human Reprod 17: 721–726.
   PubMed Web of Science ®Google Scholar
• Kadenbach, B., Huttemann, M., Arnold, S., Lee, I. and Bender, E. (2000) Mitochondrial energy metabolism is regulated via nuclear-coded subunits of cytochrome c oxidase. Free Radic Biol Med 29: 211–221.
   PubMed Web of Science ®Google Scholar
• Kamijo, T., Wanders, R., Saudubray, J., Aoyama, T., Komiyama, A. and Hashimoto, T. (1994) Mitochondrial trifunctional protein deficiency. Catalytic heterogeneity of the mutant enzyme in two patients. J Clin Invest 93: 1740.
   Google Scholar
• Larhlimi, A., David, L., Selbig, J. and Bockmayr, A. (2012) F2C2: a fast tool for the computation of flux coupling in genome-scale metabolic networks. BMC Bioinform 13: 57.
   PubMed Web of Science ®Google Scholar
• Lewis, N.E., Schramm, G., Bordbar, A., Schellenberger, J., Andersen, M.P., Cheng, J.K., et al. (2010) Large-scale in silico modeling of metabolic interactions between cell types in the human brain. Nature Biotechnol 28: 1279–1285.
   PubMed Web of Science ®Google Scholar
• Li, Y., Park, J.-S., Deng, J.-H. and Bai, Y. (2006) Cytochrome c oxidase subunit IV is essential for assembly and respiratory function of the enzyme complex. J Bioenerg Biomembranes 38: 283–291.
   PubMed Web of Science ®Google Scholar
• Liu, F.-J., Liu, X., Han, J.-L., Wang, Y.-W., Jin, S.-H., Liu, X.-X., et al. (2015) Aged men share the sperm protein PATE1 defect with young asthenozoospermia patients. Human Reprod 30: 861–869.
   PubMed Web of Science ®Google Scholar
• Luconi, M., Forti, G. and Baldi, E. (2006) Pathophysiology of sperm motility. Front Biosci 11: 1433–1447.
   PubMed Web of Science ®Google Scholar
• Mahadevan, R. and Schilling, C. (2003) The effects of alternate optimal solutions in constraint-based genome-scale metabolic models. Metab Eng 5: 264–276.
   PubMed Web of Science ®Google Scholar
• Marchetti, C., Obert, G., Deffosez, A., Formstecher, P. and Marchetti, P. (2002) Study of mitochondrial membrane potential, reactive oxygen species, DNA fragmentation and cell viability by flow cytometry in human sperm. Human Reprod 17: 1257–1265.
   PubMed Web of Science ®Google Scholar
• Mardinoglu, A. and Nielsen, J. (2012) Systems medicine and metabolic modelling. J Intern Med 271: 142–154.
   PubMed Web of Science ®Google Scholar
• Mardinoglu, A., Agren, R., Kampf, C., Asplund, A., Uhlen, M. and Nielsen, J. (2014) Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease. Nature Commun 5: 3083.
   PubMed Web of Science ®Google Scholar
• Martínez-Heredia, J., de Mateo, S., Vidal-Taboada, J.M., Ballescà, J.L. and Oliva, R. (2008) Identification of proteomic differences in asthenozoospermic sperm samples. Human Reprod 23: 783–791.
   PubMed Web of Science ®Google Scholar
• Mayr, J.A., Merkel, O., Kohlwein, S.D., Gebhardt, B.R., Böhles, H., Fötschl, U., et al. (2007) Mitochondrial Phosphate–Carrier Deficiency: A Novel Disorder of Oxidative Phosphorylation. Am J Human Genet 80: 478–484.
   PubMed Web of Science ®Google Scholar
• Montjean, D., De La Grange, P., Gentien, D., Rapinat, A., Belloc, S., Cohen-Bacrie, P., et al. (2012) Sperm transcriptome profiling in oligozoospermia. J Assisted Reprod Genet 29: 3–10.
   PubMed Web of Science ®Google Scholar
• Nayernia, K., Adham, I.M., Burkhardt-Göttges, E., Neesen, J., Rieche, M., Wolf, S., et al. (2002) Asthenozoospermia in mice with targeted deletion of the sperm mitochondrion-associated cysteine-rich protein (Smcp) gene. Mol Cell Biol 22: 3046–3052.
   PubMed Web of Science ®Google Scholar
• Nishi, T. and Forgac, M. (2002) The vacuolar (H+)-ATPases—nature’s most versatile proton pumps. Nature Reviews Mol Cell Biol 3: 94–103.
   PubMed Web of Science ®Google Scholar
• O’Brien, E.J., Monk, J.M. and Palsson, B.O. (2015) Using genome-scale models to predict biological capabilities. Cell 161: 971–987.
   PubMed Web of Science ®Google Scholar
• Orth, J.D., Thiele, I. and Palsson, B.Ø. (2010) What is flux balance analysis? Nature Biotechnol 28: 245–248.
   Google Scholar
• Ota, K., Jaiswal, M.K., Ramu, S., Jeyendran, R., Kwak-Kim, J., Gilman-Sachs, A., et al. (2013) Expression of a2 vacuolar ATPase in spermatozoa is associated with semen quality and chemokine-cytokine profiles in infertile men. PloS One 8: e70470.
   Google Scholar
• Palmieri, F. (2013) The mitochondrial transporter family SLC25: identification, properties and physiopathology. Mol Aspects Med 34: 465–484.
   PubMed Web of Science ®Google Scholar
• Palmieri, F. and Pierri, C.L. (2010) Mitochondrial metabolite transport. Essays Biochem 47: 37–52.
   PubMed Web of Science ®Google Scholar
• Pascual, M., Cebrian-Perez, J., Lopez-Perez, M. and Muino-Blanco, T. (1996) Short-term inhibition of the energy metabolism affects motility but not surface properties of sperm cells. Biosci Rep 16: 35–40.
   PubMed Web of Science ®Google Scholar
• Pereira, L., Gonçalves, J. and Bandelt, H. J. (2008) Mutation C11994T in the mitochondrial ND4 gene is not a cause of low sperm motility in Portugal. Fertil Steril 89: 738–741.
   PubMed Web of Science ®Google Scholar
• Piomboni, P., Focarelli, R., Stendardi, A., Ferramosca, A. and Zara, V. (2012) The role of mitochondria in energy production for human sperm motility. Int J Androl 35: 109–124.
   PubMedGoogle Scholar
• Rezola, A., Pey, J., Rubio, Á. and Planes, F.J. (2014) In-silico prediction of key metabolic differences between two non-small cell lung cancer subtypes. PloS One 9: e103998.
   Google Scholar
• Roy, A., Lin, Y.-N., Agno, J.E., DeMayo, F.J. and Matzuk, M.M. (2007) Absence of tektin 4 causes asthenozoospermia and subfertility in male mice. FASEB J 21: 1013–1025.
   PubMed Web of Science ®Google Scholar
• Ruiz-Pesini, E., Diez, C., Lapeña, A.C., Pérez-Martos, A., Montoya, J., Alvarez, E., et al. (1998) Correlation of sperm motility with mitochondrial enzymatic activities. Clin Chem 44: 1616–1620.
   PubMed Web of Science ®Google Scholar
• Ruiz-Pesini, E., Lapena, A.-C., Díez-Sánchez, C., Pérez-Martos, A., Montoya, J., Alvarez, E., et al. (2000) Human mtDNA haplogroups associated with high or reduced spermatozoa motility. Am J Human Genet 67: 682–696.
   PubMed Web of Science ®Google Scholar
• Ruiz‐Pesini, E., Díez‐Sánchez, C., López‐Pérez, M.J. and Enriquez, J.A. (2007) The role of the mitochondrion in sperm function: is there a place for oxidative phosphorylation or is this a purely glycolytic process? Curr Topics Dev Biol 77: 3–19.
   Google Scholar
• Ryu, J.Y., Kim, H.U. and Lee, S.Y. (2015) Reconstruction of genome-scale human metabolic models using omics data. Integr Biol 7: 859–868.
   Google Scholar
• Safarinejad, M.R., Safarinejad, S., Shafiei, N. and Safarinejad, S. (2012) Effects of the reduced form of coenzyme Q 10 (ubiquinol) on semen parameters in men with idiopathic infertility: a double-blind, placebo controlled, randomized study. J Urol 188: 526–531.
   PubMed Web of Science ®Google Scholar
• Salazar, D.A., Rodríguez-López, A., Herreño, A., Barbosa, H., Herrera, J., Ardila, A., et al. (2016) Systems biology study of mucopolysaccharidosis using a human metabolic reconstruction network. Mol Genet Metabol 117: 129–139.
   PubMed Web of Science ®Google Scholar
• Schellenberger, J., Que, R., Fleming, R.M., Thiele, I., Orth, J.D., Feist, A.M., et al. (2011) Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2. 0. Nature Protocols 6: 1290–1307.
   PubMed Web of Science ®Google Scholar
• Sharpe, R.M. (2010) Environmental/lifestyle effects on spermatogenesis. Phil Transac R Soc Lond B Biol Sci 365: 1697–1712.
   PubMed Web of Science ®Google Scholar
• Shen, S., Wang, J., Liang, J. and He, D. (2013) Comparative proteomic study between human normal motility sperm and idiopathic asthenozoospermia. World J Urol 31: 1395–1401.
   PubMed Web of Science ®Google Scholar
• Shlomi, T., Cabili, M.N. and Ruppin, E. (2009) Predicting metabolic biomarkers of human inborn errors of metabolism. Mol Syst Biol 5: 263.
   PubMed Web of Science ®Google Scholar
• Ślęzak, R., Szczepaniak, M., Pasińska, M. and Czemarmazowicz, H. (2007) The analysis of CFTR mutations in men with azoospermia, oligozoospermia and asthenozoospermia. Ginekol Pol 78: 605–610
   PubMedGoogle Scholar
• Sohrabi-Jahromi, S., Marashi, S.A. and Kalantari, S. (2016) A kidney-specific genome-scale metabolic network model for analyzing focal segmental glomerulosclerosis. Mamm Genome 27: 158–167.
   PubMed Web of Science ®Google Scholar
• Song, P., Zou, S., Chen, T., Chen, J., Wang, Y., Yang, J., et al. (2015) Endothelial nitric oxide synthase (eNOS) T-786C, 4a4b, and G894T polymorphisms and male infertility: study for idiopathic asthenozoospermia and meta-analysis. Biol Reprod 92: 38.
   PubMed Web of Science ®Google Scholar
• Sousa, A.P., Amaral, A., Baptista, M., Tavares, R., Campo, P.C., Peregrín, P.C., et al. (2011) Not all sperm are equal: functional mitochondria characterize a subpopulation of human sperm with better fertilization potential. PloS One 6: e18112.
   PubMed Web of Science ®Google Scholar
• Storey, B.T. (2008) Mammalian sperm metabolism: oxygen and sugar, friend and foe. Int J Dev Biol 52: 427.
   PubMed Web of Science ®Google Scholar
• Sun-Wada, G.-H., Imai-Senga, Y., Yamamoto, A., Murata, Y., Hirata, T., Wada, Y., et al. (2002) A proton pump ATPase with testis-specific E1-subunit isoform required for acrosome acidification. J Biol Chem 277: 18098–18105.
   PubMed Web of Science ®Google Scholar
• Sun, J., Aluvila, S., Kotaria, R., Mayor, J.A., Walters, D.E. and Kaplan, R.S. (2010) Mitochondrial and plasma membrane citrate transporters: discovery of selective inhibitors and application to structure/function analysis. Mol Cell Pharmacol 2: 101.
   PubMedGoogle Scholar
• Swainston, N., Smallbone, K., Hefzi, H., Dobson, P.D., Brewer, J., Hanscho, M., et al. (2016) Recon 2.2: from reconstruction to model of human metabolism. Metabolomics 12: 109.
   PubMed Web of Science ®Google Scholar
• Tanphaichitr, N. (1976) In vitro stimulation of human sperm motility by acetylcarnitine. International J Fertil 22: 85–91.
   Google Scholar
• Thiele, I., Swainston, N., Fleming, R.M., Hoppe, A., Sahoo, S., Aurich, M.K., et al. (2013) A community-driven global reconstruction of human metabolism. Nature Biotechnol 31: 419–425.
   PubMed Web of Science ®Google Scholar
• Tomar, A.K., Saraswat, M., Chhikara, N., Kumar, S., Yadav, V.K., Sooch, B.S., et al. (2010) Differential proteomics of sperm: insights, challenges and future prospects. Biomarkers Med 4: 905–910.
   PubMed Web of Science ®Google Scholar
• Tomar, R., Mishra, A.K., Mohanty, N.K. and Jain, A.K. (2012) Altered expression of succinic dehydrogenase in asthenozoospermia infertile male. Am J Reprod Immun 68: 486–490.
   PubMed Web of Science ®Google Scholar
• Vernejoul, F., Ghenassia, L., Souque, A., Lulka, H., Drocourt, D., Cordelier, P., et al. (2006) Gene therapy based on gemcitabine chemosensitization suppresses pancreatic tumor growth. Mol Ther 14: 758–767.
   PubMed Web of Science ®Google Scholar
• Visser, L., Westerveld, G.H., Xie, F., van Daalen, S.K., van der Veen, F., Lombardi, M.P., et al. (2011) A comprehensive gene mutation screen in men with asthenozoospermia. Fertil Steril 95: 1020–1024. e9.
   Google Scholar
• Wang, G., Guo, Y., Zhou, T., Shi, X., Yu, J., Yang, Y., et al. (2013) In-depth proteomic analysis of the human sperm reveals complex protein compositions. J Proteomics 79: 114–122.
   PubMed Web of Science ®Google Scholar
• Wang, Y., Eddy, J.A. and Price, N.D. (2012) Reconstruction of genome-scale metabolic models for 126 human tissues using mCADRE. BMC Syst Biol 13: 153.
   Web of Science ®Google Scholar
• Yi, Y.-J., Sutovsky, M., Kennedy, C. and Sutovsky, P. (2012) Identification of the inorganic pyrophosphate metabolizing, ATP substituting pathway in mammalian spermatozoa. PloS One 7: e34524.
   Google Scholar
• Yu, Q., Zhou, Q., Wei, Q., Li, J., Feng, C. and Mao, X. (2014) SEMG1 may be the candidate gene for idiopathic asthenozoospermia. Andrologia 46: 158–166.
   PubMed Web of Science ®Google Scholar
• Zhang, C. and Hua, Q. (2015) Applications of genome-scale metabolic models in biotechnology and systems medicine. Frontiers Physiol 7: 413.
   Google Scholar
• Zhao, C., Huo, R., Wang, F.-Q., Lin, M., Zhou, Z.-M. and Sha, J.-H. (2007) Identification of several proteins involved in regulation of sperm motility by proteomic analysis. Fertil Steril 87: 436–438.
   PubMed Web of Science ®Google Scholar
• Zuccarello, D., Ferlin, A., Garolla, A., Pati, M.A., Moretti, A., Cazzadore, C., et al. (2008) A possible association of a human tektin-t gene mutation (A229V) with isolated non-syndromic asthenozoospermia: case report. Human Reprod 23: 996–1001.
   PubMed Web of Science ®Google Scholar