Metabolic substrates exhibit differential effects on functional parameters of mouse sperm capacitation

Biology of Reproduction

Volumn 87, Issue 3, 2012, Pages

  Goodson, Summer G ^a   Qiu, Yunping ^b   Sutton, Keith A ^c   Xie, Guoxiang ^b   Jia, Wei ^b   O'Brien, Deborah A ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF NORTH CAROLINA AT GREENSBORO   (United States)

^c UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

Glycolysis; Metabolism; Sperm capacitation; Sperm hyperactivation; Sperm motility and transport

Indexed keywords

ADENOSINE TRIPHOSPHATE; FRUCTOSE; GLUCOSE; HYDROXYBUTYRIC ACID; MANNOSE; PYRUVIC ACID;

ANIMAL EXPERIMENT; ARTICLE; CELL PH; CONTROLLED STUDY; GLYCOLYSIS; IN VITRO STUDY; MALE; MOUSE; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; QUANTITATIVE ANALYSIS; SPERMATOZOON CAPACITATION; SPERMATOZOON MOTILITY;

ANIMALS; CELL SURVIVAL; FRUCTOSE; GLUCOSE; GLYCOLYSIS; MALE; MANNOSE; METABOLOMICS; MICE; PHOSPHORYLATION; PYRUVIC ACID; SPERM CAPACITATION; SPERM MOTILITY; SPERMATOZOA; TYROSINE;

MAMMALIA;

EID: 84869482811     PISSN: 00063363     EISSN: 15297268     Source Type: Journal    
DOI: 10.1095/biolreprod.112.102673     Document Type: Article

References (114)

1. Yanagimachi R. Mammalian fertilization. In: Knobil E, Neill J (eds.),The Physiology of Reproduction. New York: Raven Press; 1994:189-317.
2. Visconti PE, Westbrook VA, Chertihin O, Demarco I, Sleight S,Diekman AB. Novel signaling pathways involved in sperm acquisition of fertilizing capacity. J Reprod Immunol 2002; 53:133-150.
3. Rikmenspoel R. The tail movement of bull spermatozoa. Observations and model calculations. Biophys J 1965; 5:365-392.
4. Kirichok Y, Lishko PV. Rediscovering sperm ion channels with the patch-clamp technique. Mol Hum Reprod 2011; 17:478-499.
5. Fraser LR. The "switching on" of mammalian spermatozoa: molecular events involved in promotion and regulation of capacitation. Mol Reprod Dev 2009; 77:197-208.
6. Krapf D, Arcelay E, Wertheimer EV, Sanjay A, Pilder SH, Salicioni AM,Visconti PE. Inhibition of Ser/Thr phosphatases induces capacitationassociated signaling in the presence of Src kinase inhibitors. J Biol Chem 2010; 285:7977-7985.
7. Esposito G, Jaiswal BS, Xie F, Krajnc-Franken MA, Robben TJ, Strik AM, Kuil C, Philipsen RL, van Duin M, Conti M, Gossen JA. Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect. Proc Natl Acad Sci U S A 2004; 101:2993-2998.
8. Xie F, Garcia MA, Carlson AE, Schuh SM, Babcock DF, Jaiswal BS,Gossen JA, Esposito G, van Duin M, Conti M. Soluble adenylyl cyclase (sAC) is indispensable for sperm function and fertilization. Dev Biol 2006; 296:353-362.
9. Nolan MA, Babcock DF, Wennemuth G, Brown W, Burton KA,McKnight GS. Sperm-specific protein kinase A catalytic subunit Ca2 orchestrates cAMP signaling for male fertility. Proc Natl Acad Sci U S A 2004; 101:13483-13488.
10. 2+ entry into mouse sperm triggers a tail-to-head propagation. Biol Reprod 2007; 77:551-559.
11. Ren D, Navarro B, Perez G, Jackson AC, Hsu S, Shi Q, Tilly JL,Clapham DE. A sperm ion channel required for sperm motility and male fertility. Nature 2001; 413:603-609.
12. Van Dop C, Hutson SM, Lardy HA. Pyruvate metabolism in bovine epididymal spermatozoa. J Biol Chem 1977; 252:1303-1308.
13. Hammerstedt RH, Lardy HA. The effect of substrate cycling on the ATP yield of sperm glycolysis. J Biol Chem 1983; 258:8759-8768.
14. Williams AC, Ford WC. The role of glucose in supporting motility and capacitation in human spermatozoa. J Androl 2001; 22:680-695.
15. Mukai C, Okuno M. Glycolysis plays a major role for adenosine triphosphate supplementation in mouse sperm flagellar movement. Biol Reprod 2004; 71:540-547.
16. Hoskins DD. Adenine nucleotide mediation of fructolysis and motility in bovine epididymal spermatozoa. J Biol Chem 1973; 248:1135-1140.
17. Mann T, Lutwak-Mann C. Male Reproductive Function and Semen.Berlin: Springer-Verlag; 1981.
18. Miki K, Qu W, Goulding EH, Willis WD, Bunch DO, Strader LF,Perreault SD, Eddy EM, O'Brien DA. Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility. Proc Natl Acad Sci U S A 2004; 101:16501-16506.
19. Odet F, Duan C, Willis WD, Goulding EH, Kung A, Eddy EM, Goldberg E. Expression of the gene for mouse lactate dehydrogenase C (Ldhc) is required for male fertility. Biol Reprod 2008; 79:26-34.
20. Danshina PV, Geyer CB, Dai Q, Goulding EH, Willis WD, Kitto GB,McCarrey JR, Eddy EM, O'Brien DA. Phosphoglycerate kinase 2 (Pgk2) is essential for sperm function and male fertility in mice. Biol Reprod 2010; 82:136-145.
21. Narisawa S, Hecht NB, Goldberg E, Boatright KM, Reed JC, Millan JL.Testis-specific cytochrome c-null mice produce functional sperm but undergo early testicular atrophy. Mol Cell Biol 2002; 22:5554-5562.
22. Peterson RN, Freund M. ATP synthesis and oxidative metabolism in human spermatozoa. Biol Reprod 1970; 3:47-54.
23. Suter D, Chow PY, Martin IC. Maintenance of motility in human spermatozoa by energy derived through oxidative phosphorylation and addition of albumin. Biol Reprod 1979; 20:505-510.
24. Ford WC, Harrison A. The role of oxidative phosphorylation in the generation of ATP in human spermatozoa. J Reprod Fertil 1981; 63:271-278.
25. Tanaka H, Takahashi T, Iguchi N, Kitamura K, Miyagawa Y, Tsujimura A, Matsumiya K, Okuyama A, Nishimune Y. Ketone bodies could support the motility but not the acrosome reaction of mouse sperm. Int J Androl 2004; 27:172-177.
26. Cooper TG. The onset and maintenance of hyperactivated motility of spermatozoa in the mouse. Gamete Res 1984; 9:55-74.
27. Cao W, Aghajanian HK, Haig-Ladewig LA, Gerton GL. Sorbitol can fuel mouse sperm motility and protein tyrosine phosphorylation via sorbitol dehydrogenase. Biol Reprod 2009; 80:124-133.
28. Storey BT. Mammalian sperm metabolism: oxygen and sugar, friend and foe. Int J Dev Biol 2008; 52:427-437.
29. Eddy EM, Toshimori K, O'Brien DA. Fibrous sheath of mammalian spermatozoa. Microsc Res Tech 2003; 61:103-115.
30. Krisfalusi M, Miki K, Magyar PL, O'Brien DA. Multiple glycolytic enzymes are tightly bound to the fibrous sheath of mouse spermatozoa.Biol Reprod 2006; 75:270-278.
31. Boer PH, Adra CN, Lau YF, McBurney MW. The testis-specific phosphoglycerate kinase gene pgk-2 is a recruited retroposon. Mol Cell Biol 1987; 7:3107-3112.
32. McCarrey JR, Thomas K. Human testis-specific Pgk gene lacks introns and possesses characteristics of a processed gene. Nature 1987; 326:501-505.
33. Millan JL, Driscoll CE, LeVan KM, Goldberg E. Epitopes of human testis-specific lactate dehydrogenase deduced from a cDNA sequence.Proc Natl Acad Sci U S A 1987; 84:5311-5315.
34. Welch JE, Schatte EC, O'Brien DA, Eddy EM. Expression of a glyceraldehyde 3-phosphate dehydrogenase gene specific to mouse spermatogenic cells. Biol Reprod 1992; 46:869-878.
35. Mori C, Welch JE, Fulcher KD, O'Brien DA, Eddy EM. Unique hexokinase messenger ribonucleic acids lacking the porin-binding domain are developmentally expressed in mouse spermatogenic cells.Biol Reprod 1993; 49:191-203.
36. Vemuganti SA, Bell TA, Scarlett CO, Parker CE, de Villena FP, O'Brien DA. Three male germline-specific aldolase A isozymes are generated by alternative splicing and retrotransposition. Dev Biol 2007; 309:18-31.
37. Hennig B. Change of cytochrome c structure during development of the mouse. Eur J Biochem 1975; 55:167-183.
38. Tanaka H, Iguchi N, Miyagawa Y, Koga M, Kohroki J, Nishimune Y.Differential expression of succinyl CoA transferase (SCOT) genes in somatic and germline cells of the mouse testis. Int J Androl 2003; 26:52-56.
39. Mitra K, Rangaraj N, Shivaji S. Novelty of the pyruvate metabolic enzyme dihydrolipoamide dehydrogenase in spermatozoa: correlation of its localization, tyrosine phosphorylation, and activity during sperm capacitation. J Biol Chem 2005; 280:25743-25753.
40. Goodson SG, Zhang Z, Tsuruta JK, Wang W, O'Brien DA. Classification of mouse sperm motility patterns using an automated multiclass support vector machines model. Biol Reprod 2011; 84:1207-1215.
41. Byers SL, Payson SJ, Taft RA. Performance of ten inbred mouse strains following assisted reproductive technologies (ARTs). Theriogenology 2006; 65:1716-1726.
42. Quinn P, Kerin JF, Warnes GM. Improved pregnancy rate in human in vitro fertilization with the use of a medium based on the composition of human tubal fluid. Fertil Steril 1985; 44:493-498.
43. Garner DL, Johnson LA. Viability assessment of mammalian sperm using SYBR-14 and propidium iodide. Biol Reprod 1995; 53:276-284.
44. Kalab P, Visconti P, Leclerc P, Kopf GS. p95, the major phosphotyrosine-containing protein in mouse spermatozoa, is a hexokinase with unique properties. J Biol Chem 1994; 269:3810-3817.
45. Koppers AJ, De Iuliis GN, Finnie JM, McLaughlin EA, Aitken RJ.Significance of mitochondrial reactive oxygen species in the generation of oxidative stress in spermatozoa. J Clin Endocrinol Metab 2008; 93:3199-3207.
46. 2+ influx. Biol Reprod 2007; 76:660-665.
47. Fordahl S, Cooney P, Qiu Y, Xie G, Jia W, Erikson KM. Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors. Neurotoxicol Teratol 2012; 34:27-36.
48. Qiu Y, Cai G, Su M, Chen T, Zheng X, Xu Y, Ni Y, Zhao A, Xu LX, Cai S, Jia W. Serum metabolite profiling of human colorectal cancer using GC-TOFMS and UPLC-QTOFMS. J Proteome Res 2009; 8:4844-4850.
49. Ecroyd H, Jones RC, Aitken RJ. Endogenous redox activity in mouse spermatozoa and its role in regulating the tyrosine phosphorylation events associated with sperm capacitation. Biol Reprod 2003; 69:347-354.
50. Aitken RJ, Ryan AL, Baker MA, McLaughlin EA. Redox activity associated with the maturation and capacitation of mammalian spermatozoa. Free Radic Biol Med 2004; 36:994-1010.
51. Vernet P, Fulton N, Wallace C, Aitken RJ. Analysis of reactive oxygen species generating systems in rat epididymal spermatozoa. Biol Reprod 2001; 65:1102-1113.
52. Lewis B, Aitken RJ. A redox-regulated tyrosine phosphorylation cascade in rat spermatozoa. J Androl 2001; 22:611-622.
53. Medrano A, Fernandez-Novell JM, Ramio L, Alvarez J, Goldberg E,Montserrat Rivera M, Guinovart JJ, Rigau T, Rodriguez-Gil JE.Utilization of citrate and lactate through a lactate dehydrogenase and ATP-regulated pathway in boar spermatozoa. Mol Reprod Dev 2006; 73:369-378.
54. Rigau T, Rivera M, Palomo MJ, Fernandez-Novell JM, Mogas T,Ballester J, Pena A, Otaegui PJ, Guinovart JJ, Rodriguez-Gil JE.Differential effects of glucose and fructose on hexose metabolism in dog spermatozoa. Reproduction 2002; 123:579-591.
55. Niwa K, Iritani A. Effect of various hexoses on sperm capacitation and penetration of rat eggs in vitro. J Reprod Fertil 1978; 53:267-271.
56. Visconti PE, Bailey JL, Moore GD, Pan D, Olds-Clarke P, Kopf GS.Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation. Development 1995; 121:1129-1137.
57. Travis AJ, Jorgez CJ, Merdiushev T, Jones BH, Dess DM, Diaz-Cueto L,Storey BT, Kopf GS, Moss SB. Functional relationships between capacitation-dependent cell signaling and compartmentalized metabolic pathways in murine spermatozoa. J Biol Chem 2001; 276:7630-7636.
58. 2+ signaling pathways modulate sperm flagellar beating patterns in mice. Biol Reprod 2011; 85:296-305.
59. Lishko PV, Kirichok Y. The role of Hv1 and CatSper channels in sperm activation. J Physiol 2010; 588:4667-4672.
60. i. J Biol Chem 1992; 267:7545-7552.
61. - -dependent and arylaminobenzoate- dependent regulatory mechanisms and characterization of their roles in sperm capacitation.Dev Biol 1996; 173:510-520.
62. Vredenburgh-Wilberg WL, Parrish JJ. Intracellular pH of bovine sperm increases during capacitation. Mol Reprod Dev 1995; 40:490-502.
63. Cross NL, Razy-Faulkner P. Control of human sperm intracellular pH by cholesterol and its relationship to the response of the acrosome to progesterone. Biol Reprod 1997; 56:1169-1174.
64. Okabe M, Adachi T, Kohama Y, Mimura T. Effect of glucose and phloretin-2'-beta-d-glucose (phloridzin) on in vitro fertilization of mouse ova. Experientia 1986; 42:398-399.
65. Nazzaro-Porro M, Passi S. Identification of tyrosinase inhibitors in cultures of Pityrosporum. J Invest Dermatol 1978; 71:205-208.
66. Passi S, Picardo M, Nazzaro-Porro M, Breathnach A, Confaloni AM, Serlupi-Crescenzi G. Antimitochondrial effect of saturated medium chain length (C8-C13) dicarboxylic acids. Biochem Pharmacol 1984; 33: 103-108.
67. Zompetta C, De Luca C, Breathnach AS, Nazzaro-Porro M. The oxyradical-scavenging activity of azelaic acid in biological systems. Free Radic Res Commun 1991; 15:17-28.
68. Bargoni N, Tazartes O. On the effect of aliphatic saturated dicarboxylic acids on anaerobic glycolysis in chicken embryo. Ital J Biochem 1983; 32:385-390.
69. Schallreuter KU, Wood JM. Azelaic acid as a competitive inhibitor of thioredoxin reductase in human melanoma cells. Cancer Lett 1987; 36: 297-305.
70. Huxtable RJ. Physiological actions of taurine. Physiol Rev 1992; 72: 101-163.
71. Holmes RP, Goodman HO, Shihabi ZK, Jarow JP. The taurine and hypotaurine content of human semen. J Androl 1992; 13:289-292.
72. +-ATPase activity by taurine and hypotaurine. Life Sci 1985; 36:271-275.
73. Alvarez JG, Storey BT. Lipid peroxidation and the reactions of superoxide and hydrogen peroxide in mouse spermatozoa. Biol Reprod 1984; 30:833-841.
74. Quinn PJ, Boldyrev AA, Formazuyk VE. Carnosine: Its properties,functions, and potential therapeutic applications. Mol Aspects Med 1992;13:379-444.
75. Sanchez-Partida LG, Setchell BP, Maxwell WM. Epididymal compounds and antioxidants in diluents for the frozen storage of ram spermatozoa. Reprod Fertil Dev 1997; 9:689-696.
76. Babizhayev MA, Costa EB. Lipid peroxide and reactive oxygen species generating systems of the crystalline lens. Biochim Biophys Acta 1994;1225:326-337.
77. Babizhayev MA, Seguin MC, Gueyne J, Evstigneeva RP, Ageyeva EA, Zheltukhina GA. l-Carnosine (beta-alanyl-l-histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radicalscavenging and lipid-peroxidase activities.Biochem J 1994; 304(pt 2): 509-516.
78. Kang JH, Kim KS, Choi SY, Kwon HY, Won MH, Kang TC. Carnosine and related dipeptides protect human ceruloplasmin against peroxyl radical-mediated modification. Mol Cells 2002; 13:498-502.
79. MacDonald MJ. Differences between mouse and rat pancreatic islets: succinate responsiveness, malic enzyme, and anaplerosis. Am J Physiol Endocrinol Metab 2002; 283:E302-E310.
80. Yang L, Kasumov T, Kombu RS, Zhu SH, Cendrowski AV, David F, Anderson VE, Kelleher JK, Brunengraber H. Metabolomic and mass isotopomer analysis of liver gluconeogenesis and citric acid cycle: II. Heterogeneity of metabolite labeling pattern. J Biol Chem 2008; 283: 21988-21996.
81. Awda BJ, Buhr MM. Extracellular signal-regulated kinases (ERKs) pathway and reactive oxygen species regulate tyrosine phosphorylation in capacitating boar spermatozoa. Biol Reprod 2010; 83:750-758.
82. Dona G, Fiore C, Tibaldi E, Frezzato F, Andrisani A, Ambrosini G, Fiorentin D Armanini D, Bordin L, Clari G. Endogenous reactive oxygen species content and modulation of tyrosine phosphorylation during sperm capacitation. Int J Androl 2011; 34:411-419.
83. Griveau JF, Renard, P, Le Lannou, D. An in vitro promoting role for hydrogen peroxide in human sperm capacitation. Int J Androl 1994; 17: 300-307.
84. Hoppe PC. Glucose requirement for mouse sperm capacitation in vitro.Biol Reprod 1976; 15:39-45.
85. Summers MC, Biggers JD. Chemically defined media and the culture of mammalian preimplantation embryos: historical perspective and current issues. Hum Reprod Update 2003; 9:557-582.
86. Fraser LR, Quinn PJ. A glycolytic product is obligatory for initiation of the sperm acrosome reaction and whiplash motility required for fertilization in the mouse. J Reprod Fertil 1981; 61:25-35.
87. Urner F, Leppens-Luisier G, Sakkas D. Protein tyrosine phosphorylation in sperm during gamete interaction in the mouse: the influence of glucose. Biol Reprod 2001; 64:1350-1357.
88. Carrera A, Moos J, Ning XP, Gerton GL, Tesarik J, Kopf GS, Moss SB. Regulation of protein tyrosine phosphorylation in human sperm by a calcium/calmodulin-dependent mechanism: identification of A kinase anchor proteins as major substrates for tyrosine phosphorylation. Dev Biol 1996; 180:284-296.
89. Kota V, Dhople VM, Shivaji S. Tyrosine phosphoproteome of hamster spermatozoa: role of glycerol-3-phosphate dehydrogenase 2 in sperm capacitation. Proteomics 2009; 9:1809-1826.
90. Baker MA, Hetherington L, Aitken RJ. Identification of SRC as a key PKA-stimulated tyrosine kinase involved in the capacitation-associated hyperactivation of murine spermatozoa. J Cell Sci 2006; 119:3182-3192.
91. Ficarro S, Chertihin O, Westbrook VA, White F, Jayes F, Kalab P, Marto JA, Shabanowitz J, Herr JC, Hunt DF, Visconti PE. Phosphoproteome analysis of capacitated human sperm. Evidence of tyrosine phosphorylation of a kinase-anchoring protein 3 and valosin-containing protein/p97 during capacitation. J Biol Chem 2003; 278:11579-11589.
92. Arcelay E, Salicioni AM, Wertheimer E, Visconti PE. Identification of proteins undergoing tyrosine phosphorylation during mouse sperm capacitation. Int J Dev Biol 2008; 52:463-472.
93. Fraser LR, Herod JE. Expression of capacitation-dependent changes in chlortetracycline fluorescence patterns in mouse spermatozoa requires a suitable glycolysable substrate. J Reprod Fertil 1990; 88:611-621.
94. 14 to liver and muscle glycogen in the rat. J Biol Chem 1955; 214:373-381.
95. Tappy L, Le KA. Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev 2010; 90:23-46.
96. Carey JE, Olds-Clarke P, Storey BT. Oxidative metabolism of spermatozoa from inbred and random bred mice. J Exp Zool 1981;216:285-292.
97. Terada H. The interaction of highly active uncouplers with mitochondria. Biochim Biophys Acta 1981; 639:225-242.
98. James-Kracke MR. Quick and accurate method to convert BCECF fluorescence to pHi: calibration in three different types of cell preparations. J Cell Physiol 1992; 151:596-603.
99. Tahara EB, Navarete FD, Kowaltowski AJ. Tissue-, substrate-, and sitespecific characteristics of mitochondrial reactive oxygen species generation. Free Radic Biol Med 2009; 46:1283-1297.
100. 2+ channel of human sperm. Nature 2011; 471:387-391.
101. + exchanger. Mol Reprod Dev 1999; 52:189-195.
102. 2+ channel. Nature 2006; 439:737-740.
103. Semchyshyn HM, Lozinska LM, Miedzobrodzki J, Lushchak VI.Fructose and glucose differentially affect aging and carbonyl/oxidative stress parameters in Saccharomyces cerevisiae cells. Carbohydr Res 2011; 346:933-938.
104. Cirillo P, Gersch MS, Mu W, Scherer PM, Kim KM, Gesualdo L, Henderson GN, Johnson RJ, Sautin YY. Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators in proximaltubular cells. J Am Soc Nephrol 2009; 20:545-553.
105. Mann T. Secretory function of the prostate, seminal vesicle and other male accessory organs of reproduction. J Reprod Fertil 1974; 37:179-188.
106. Marchlewska-Koj A. Fructose content of mouse ejaculates recovered from the uterus after mating. J Reprod Fertil 1971; 25:81-84.
107. Anderson RA Jr, Oswald C, Willis BR, Zaneveld LJ. Relationship between semen characteristics and fertility in electroejaculated mice. J Reprod Fertil 1983; 68:1-7.
108. Pascqualotto FF, Sharma RK, Nelson DR, Thomas AJ Jr, Agarwal A.Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation. Fertil Steril 2000;73:459-464.
109. Miraglia E, Lussiana C, Viarisio D, Racca C, Cipriani A, Gazzano E,Bosia A, Revelli A, Ghigo D. The pentose phosphate pathway plays an essential role in supporting human sperm capacitation. Fertil Steril 2010;93:2437-2440.
110. Urner F, Sakkas D. Involvement of the pentose phosphate pathway and redox regulation in fertilization in the mouse. Mol Reprod Dev 2005; 70:494-503.
111. Alvarez JG, Storey BT. Taurine, hypotaurine, epinephrine, and albumin inhibit lipid peroxidation in rabbit spermatozoa and protect against loss of motility. Biol Reprod 1983; 29:548-555.
112. de Lamirande E, O'Flaherty C. Sperm activation: role of reactive oxygen species and kinases. Biochim Biophys Acta 2008; 1784:106-115.
113. Baker MA, Aitken RJ. The importance of redox-regulated pathways in sperm cell biology. Mol Cell Endocrinol 2004; 216:47-54.
114. Aitken RJ, Harkiss D, Knox W, Paterson M, Irvine DS. A novel signal transduction cascade in capacitating human spermatozoa characterized by a redox-regulated, cAMP-mediated induction of tyrosine phosphorylation.J Cell Sci 1998; 111(pt 5):645-656.