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Home / Equine Research Bank / Biol Reprod / Guanine-nucleotide exchange factors (RAPGEF3/RAPGEF4) induce...
Biology of reproduction2011; 85(1); 179-188; doi: 10.1095/biolreprod.110.085555

Guanine-nucleotide exchange factors (RAPGEF3/RAPGEF4) induce sperm membrane depolarization and acrosomal exocytosis in capacitated stallion sperm.

Abstract: Capacitation encompasses the molecular changes sperm undergo to fertilize an oocyte, some of which are postulated to occur via a cAMP-PRKACA (protein kinase A)-mediated pathway. Due to the recent discovery of cAMP-activated guanine nucleotide exchange factors RAPGEF3 and RAPGEF4, we sought to investigate the separate roles of PRKACA and RAPGEF3/RAPGEF4 in modulating capacitation and acrosomal exocytosis. Indirect immunofluorescence localized RAPGEF3 to the acrosome and subacrosomal ring and RAPGEF4 to the midpiece in equine sperm. Addition of the RAPGEF3/RAPGEF4-specific cAMP analogue 8-(p-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (8pCPT) to sperm incubated under both noncapacitating and capacitating conditions had no effect on protein tyrosine phosphorylation, thus supporting a PRKACA-mediated event. Conversely, activation of RAPGEF3/RAPGEF4 with 8pCPT induced acrosomal exocytosis in capacitated equine sperm at rates (34%) similar (P > 0.05) to those obtained in progesterone- and calcium ionophore-treated sperm. In the mouse, capacitation-dependent hyperpolarization of the sperm plasma membrane has been shown to recruit low voltage-activated T-type Ca(2+) channels, which later open in response to zona pellucida-induced membrane depolarization. We hypothesized that RAPGEF3 may be inducing acrosomal exocytosis via depolarization-dependent Ca(2+) influx, as RAPGEF3/RAPGEF4 have been demonstrated to play a role in the regulation of ion channels in somatic cells. We first compared the membrane potential (E(m)) of noncapacitated (-37.11 mV) and capacitated (-53.74 mV; P = 0.002) equine sperm. Interestingly, when sperm were incubated (6 h) under capacitating conditions in the presence of 8pCPT, E(m) remained depolarized (-32.06 mV). Altogether, these experiments support the hypothesis that RAPGEF3/RAPGEF4 activation regulates acrosomal exocytosis via its modulation of E(m), a novel role for RAPGEF3/RAPGEF4 in the series of events required to achieve fertilization.
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Publication Date: 2011-04-06 PubMed ID: 21471298PubMed Central: PMC3123385DOI: 10.1095/biolreprod.110.085555Google Scholar: Lookup
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  • Journal Article
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  • N.I.H.
  • Extramural
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  • Non-U.S. Gov't
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the role of certain proteins, RAPGEF3 and RAPGEF4, and how they influence the necessary changes sperm undergo (known as capacitation) to fertilise an oocyte (egg cell). It suggests these proteins regulate the process of acrosomal exocytosis, required for fertilisation, through control of membrane potential.

Understanding the Research

  • The main focus of the study is to explore the roles of the recently discovered proteins, RAPGEF3 and RAPGEF4, in sperm capacitation and acrosomal exocytosis.
  • Sperm capacitation refers to the biological changes a sperm cell undergoes to gain the ability to penetrate and fertilize an egg cell. It’s a crucial step in mammalian fertilization.
  • RAPGEF3 and RAPGEF4 are guanine nucleotide exchange factors which, in this context, are thought to be regulators of the processes involved in sperm capacitation.

Key Findings

  • The research identified the locations of RAPGEF3 and RAPGEF4 in equine sperm. RAPGEF3 was found in the acrosome and subacrosomal ring, and RAPGEF4 in the midpiece.
  • When the researchers activated RAPGEF3/RAPGEF4 in sperm, it induced acrosomal exocytosis at a rate similar to those obtained with other treatments. Acrosomal exocytosis refers to the release of enzymes from the acrosome, a structure in the sperm head, which helps the sperm penetrate the egg.
  • Another significant finding is the potential role of RAPGEF3/RAPGEF4 in the regulation of membrane potential (Em), the difference in voltage across a cell membrane. This observation adds a novel role to these proteins in the process of sperm capacitation and acrosomal exocytosis.
  • The study found that the membrane potential was different between noncapacitated and capacitated sperm. Interestingly, when RAPGEF3/RAPGEF4 were activated under capacitating conditions, the membrane potential remained depolarized, suggesting a role for these proteins in this process.

Conclusion and Implications

  • Given these findings, it’s suggested that RAPGEF3/RAPGEF4 play crucial and previously unidentified roles in the sequence of events that allow the sperm to achieve fertilisation.
  • This new knowledge contributes to the larger understanding of the molecular processes involved in sperm capacitation, and could guide future research and advances in fertility treatments.

Cite This Article

APA
McPartlin LA, Visconti PE, Bedford-Guaus SJ. (2011). Guanine-nucleotide exchange factors (RAPGEF3/RAPGEF4) induce sperm membrane depolarization and acrosomal exocytosis in capacitated stallion sperm. Biol Reprod, 85(1), 179-188. https://doi.org/10.1095/biolreprod.110.085555

Publication

Biology of reproduction
ISSN: 1529-7268
NlmUniqueID: 0207224
Country: United States
Language: English
Volume: 85
Issue: 1
Pages: 179-188

Researcher Affiliations

McPartlin, L A
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Visconti, P E
    Bedford-Guaus, S J

      MeSH Terms

      • Acrosome / physiology
      • Animals
      • Cyclic AMP / analogs & derivatives
      • Cyclic AMP / metabolism
      • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / antagonists & inhibitors
      • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / metabolism
      • Dichlororibofuranosylbenzimidazole / analogs & derivatives
      • Exocytosis
      • Guanine Nucleotide Exchange Factors / metabolism
      • Horses / metabolism
      • Male
      • Membrane Potentials
      • Mice
      • Phosphorylation
      • Protein-Tyrosine Kinases / metabolism
      • Signal Transduction
      • Sperm Capacitation
      • Thionucleotides

      Grant Funding

      • R01 HD038082 / NICHD NIH HHS
      • R01 HD044044 / NICHD NIH HHS
      • HD38082 / NICHD NIH HHS
      • HD44044 / NICHD NIH HHS

      References

      This article includes 49 references
      1. Yanagimachi R. Mammalian Fertilization. The Physiology of Reproduction 1994: 189 317.
      2. Galantino-Homer HL, Visconti PE, Kopf GS. Regulation of protein tyrosine phosphorylation during bovine sperm capacitation by a cyclic adenosine 3'5'-monophosphate-dependent pathway.. Biol Reprod 1997 Mar;56(3):707-19.
        pubmed: 9047017doi: 10.1095/biolreprod56.3.707google scholar: lookup
      3. Visconti PE, Stewart-Savage J, Blasco A, Battaglia L, Miranda P, Kopf GS, Tezón JG. Roles of bicarbonate, cAMP, and protein tyrosine phosphorylation on capacitation and the spontaneous acrosome reaction of hamster sperm.. Biol Reprod 1999 Jul;61(1):76-84.
        pubmed: 10377034doi: 10.1095/biolreprod61.1.76google scholar: lookup
      4. Osheroff JE, Visconti PE, Valenzuela JP, Travis AJ, Alvarez J, Kopf GS. Regulation of human sperm capacitation by a cholesterol efflux-stimulated signal transduction pathway leading to protein kinase A-mediated up-regulation of protein tyrosine phosphorylation.. Mol Hum Reprod 1999 Nov;5(11):1017-26.
        pubmed: 10541563doi: 10.1093/molehr/5.11.1017google scholar: lookup
      5. Visconti PE, Galantino-Homer H, Ning X, Moore GD, Valenzuela JP, Jorgez CJ, Alvarez JG, Kopf GS. Cholesterol efflux-mediated signal transduction in mammalian sperm. beta-cyclodextrins initiate transmembrane signaling leading to an increase in protein tyrosine phosphorylation and capacitation.. J Biol Chem 1999 Jan 29;274(5):3235-42.
        pubmed: 9915865doi: 10.1074/jbc.274.5.3235google scholar: lookup
      6. 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 Jan;53(1-2):133-50.
        pubmed: 11730911doi: 10.1016/s0165-0378(01)00103-6google scholar: lookup
      7. Suarez SS. Control of hyperactivation in sperm.. Hum Reprod Update 2008 Nov-Dec;14(6):647-57.
        pubmed: 18653675doi: 10.1093/humupd/dmn029google scholar: lookup
      8. Pommer AC, Rutllant J, Meyers SA. Phosphorylation of protein tyrosine residues in fresh and cryopreserved stallion spermatozoa under capacitating conditions.. Biol Reprod 2003 Apr;68(4):1208-14.
        pubmed: 12606471doi: 10.1095/biolreprod.102.011106google scholar: lookup
      9. Ellington JE, Ball BA, Blue BJ, Wilker CE. Capacitation-like membrane changes and prolonged viability in vitro of equine spermatozoa cultured with uterine tube epithelial cells.. Am J Vet Res 1993 Sep;54(9):1505-10.
        pubmed: 8239141
      10. Rathi R, Colenbrander B, Stout TA, Bevers MM, Gadella BM. Progesterone induces acrosome reaction in stallion spermatozoa via a protein tyrosine kinase dependent pathway.. Mol Reprod Dev 2003 Jan;64(1):120-8.
        pubmed: 12420307doi: 10.1002/mrd.10216google scholar: lookup
      11. Christensen P, Whitfield CH, Parkinson TJ. In vitro induction of acrosome reactions in stallion spermatozoa by heparin and A23187.. Theriogenology 1996 Apr 15;45(6):1201-10.
        pubmed: 16727876doi: 10.1016/0093-691x(96)00075-1google scholar: lookup
      12. Meyers S, Kiu I, Overstreet J, Drobins E. Induction of acrosome reactions in stallion sperm by equine zona pellucida, porcine zona pellucida, and progesterone. Biol Reprod Mono 1995; 1: 739 744.
      13. Varner DD, Ward CR, Storey BT, Kenney RM. Induction and characterization of acrosome reaction in equine spermatozoa.. Am J Vet Res 1987 Sep;48(9):1383-9.
        pubmed: 3116891
      14. Hinrichs K, Love CC, Brinsko SP, Choi YH, Varner DD. In vitro fertilization of in vitro-matured equine oocytes: effect of maturation medium, duration of maturation, and sperm calcium ionophore treatment, and comparison with rates of fertilization in vivo after oviductal transfer.. Biol Reprod 2002 Jul;67(1):256-62.
        pubmed: 12080025doi: 10.1095/biolreprod67.1.256google scholar: lookup
      15. Zhang JJ, Muzs LZ, Boyle MS. In vitro fertilization of horse follicular oocytes matured in vitro.. Mol Reprod Dev 1990 Aug;26(4):361-5.
        pubmed: 2223085doi: 10.1002/mrd.1080260411google scholar: lookup
      16. Dell'aquila ME, Fusco S, Lacalandra GM, Maritato F. In vitro maturation and fertilization of equine oocytes recovered during the breeding season.. Theriogenology 1996 Feb;45(3):547-60.
        pubmed: 16727818doi: 10.1016/0093-691x(95)00402-tgoogle scholar: lookup
      17. Dell'Aquila ME, Cho YS, Minoia P, Traina V, Lacalandra GM, Maritato F. Effects of follicular fluid supplementation of in-vitro maturation medium on the fertilization and development of equine oocytes after in-vitro fertilization or intracytoplasmic sperm injection.. Hum Reprod 1997 Dec;12(12):2766-72.
        pubmed: 9455850doi: 10.1093/humrep/12.12.2766google scholar: lookup
      18. Dell'Aquila ME, Cho YS, Minoia P, Traina V, Fusco S, Lacalandra GM, Maritato F. Intracytoplasmic sperm injection (ICSI) versus conventional IVF on abattoir-derived and in vitro-matured equine oocytes.. Theriogenology 1997 Apr 15;47(6):1139-56.
        pubmed: 16728064doi: 10.1016/s0093-691x(97)00095-2google scholar: lookup
      19. Choi YH, Okada Y, Hochi S, Braun J, Sato K, Oguri N. In vitro fertilization rate of horse oocytes with partially removed zonae.. Theriogenology 1994 Oct;42(5):795-802.
        pubmed: 16727585doi: 10.1016/0093-691x(94)90448-rgoogle scholar: lookup
      20. Alm H, Torner H, Blottner S, Nürnberg G, Kanitz W. Effect of sperm cryopreservation and treatment with calcium ionophore or heparin on in vitro fertilization of horse oocytes.. Theriogenology 2001 Sep 15;56(5):817-29.
        pubmed: 11665884doi: 10.1016/s0093-691x(01)00610-0google scholar: lookup
      21. McPartlin LA, Littell J, Mark E, Nelson JL, Travis AJ, Bedford-Guaus SJ. A defined medium supports changes consistent with capacitation in stallion sperm, as evidenced by increases in protein tyrosine phosphorylation and high rates of acrosomal exocytosis.. Theriogenology 2008 Mar 15;69(5):639-50.
        pubmed: 18242679doi: 10.1016/j.theriogenology.2007.11.016google scholar: lookup
      22. Visconti PE, Kopf GS. Regulation of protein phosphorylation during sperm capacitation.. Biol Reprod 1998 Jul;59(1):1-6.
        pubmed: 9674985doi: 10.1095/biolreprod59.1.1google scholar: lookup
      23. Visconti PE, Moore GD, Bailey JL, Leclerc P, Connors SA, Pan D, Olds-Clarke P, Kopf GS. Capacitation of mouse spermatozoa. II. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway.. Development 1995 Apr;121(4):1139-50.
        pubmed: 7538069doi: 10.1242/dev.121.4.1139google scholar: lookup
      24. Hess KC, Jones BH, Marquez B, Chen Y, Ord TS, Kamenetsky M, Miyamoto C, Zippin JH, Kopf GS, Suarez SS, Levin LR, Williams CJ, Buck J, Moss SB. The "soluble" adenylyl cyclase in sperm mediates multiple signaling events required for fertilization.. Dev Cell 2005 Aug;9(2):249-59.
        pmc: PMC3082461pubmed: 16054031doi: 10.1016/j.devcel.2005.06.007google scholar: lookup
      25. Holz GG, Kang G, Harbeck M, Roe MW, Chepurny OG. Cell physiology of cAMP sensor Epac.. J Physiol 2006 Nov 15;577(Pt 1):5-15.
        pmc: PMC2000694pubmed: 16973695doi: 10.1113/jphysiol.2006.119644google scholar: lookup
      26. Amano R, Lee J, Goto N, Harayama H. Evidence for existence of cAMP-Epac signaling in the heads of mouse epididymal spermatozoa.. J Reprod Dev 2007 Feb;53(1):127-33.
        pubmed: 17077580doi: 10.1262/jrd.18077google scholar: lookup
      27. Branham MT, Mayorga LS, Tomes CN. Calcium-induced acrosomal exocytosis requires cAMP acting through a protein kinase A-independent, Epac-mediated pathway.. J Biol Chem 2006 Mar 31;281(13):8656-66.
        pubmed: 16407249doi: 10.1074/jbc.m508854200google scholar: lookup
      28. Aivatiadou E, Ripolone M, Brunetti F, Berruti G. cAMP-Epac2-mediated activation of Rap1 in developing male germ cells: RA-RhoGAP as a possible direct down-stream effector.. Mol Reprod Dev 2009 Apr;76(4):407-16.
        pubmed: 18937323doi: 10.1002/mrd.20963google scholar: lookup
      29. Walsh DA, Ashby CD, Gonzalez C, Calkins D, Fischer EH. Krebs EG: Purification and characterization of a protein inhibitor of adenosine 3',5'-monophosphate-dependent protein kinases.. J Biol Chem 1971 Apr 10;246(7):1977-85.
        pubmed: 4324557
      30. Smolenski A, Bachmann C, Reinhard K, Hönig-Liedl P, Jarchau T, Hoschuetzky H, Walter U. Analysis and regulation of vasodilator-stimulated phosphoprotein serine 239 phosphorylation in vitro and in intact cells using a phosphospecific monoclonal antibody.. J Biol Chem 1998 Aug 7;273(32):20029-35.
        pubmed: 9685341doi: 10.1074/jbc.273.32.20029google scholar: lookup
      31. Kang G, Chepurny OG, Malester B, Rindler MJ, Rehmann H, Bos JL, Schwede F, Coetzee WA, Holz GG. cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells.. J Physiol 2006 Jun 15;573(Pt 3):595-609.
        pmc: PMC1779745pubmed: 16613879doi: 10.1113/jphysiol.2006.107391google scholar: lookup
      32. 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 Mar 9;276(10):7630-6.
        pubmed: 11115497doi: 10.1074/jbc.m006217200google scholar: lookup
      33. Holmquist L. Surface modification of Beckman Ultra-Clear centrifuge tubes for density gradient centrifugation of lipoproteins.. J Lipid Res 1982 Nov;23(8):1249-50.
        pubmed: 7175383
      34. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.. Nature 1970 Aug 15;227(5259):680-5.
        pubmed: 5432063doi: 10.1038/227680a0google scholar: lookup
      35. Arcelay E, Salicioni AM, Wertheimer E, Visconti PE. Identification of proteins undergoing tyrosine phosphorylation during mouse sperm capacitation.. Int J Dev Biol 2008;52(5-6):463-72.
        pubmed: 18649259doi: 10.1387/ijdb.072555eagoogle scholar: lookup
      36. Selvaraj V, Buttke DE, Asano A, McElwee JL, Wolff CA, Nelson JL, Klaus AV, Hunnicutt GR, Travis AJ. GM1 dynamics as a marker for membrane changes associated with the process of capacitation in murine and bovine spermatozoa.. J Androl 2007 Jul-Aug;28(4):588-99.
        pubmed: 17377143doi: 10.2164/jandrol.106.002279google scholar: lookup
      37. Jungnickel MK, Marrero H, Birnbaumer L, Lémos JR, Florman HM. Trp2 regulates entry of Ca2+ into mouse sperm triggered by egg ZP3.. Nat Cell Biol 2001 May;3(5):499-502.
        pubmed: 11331878doi: 10.1038/35074570google scholar: lookup
      38. Demarco IA, Espinosa F, Edwards J, Sosnik J, De La Vega-Beltran JL, Hockensmith JW, Kopf GS, Darszon A, Visconti PE. Involvement of a Na+/HCO-3 cotransporter in mouse sperm capacitation.. J Biol Chem 2003 Feb 28;278(9):7001-9.
        pubmed: 12496293doi: 10.1074/jbc.m206284200google scholar: lookup
      39. Hernández-González EO, Sosnik J, Edwards J, Acevedo JJ, Mendoza-Lujambio I, López-González I, Demarco I, Wertheimer E, Darszon A, Visconti PE. Sodium and epithelial sodium channels participate in the regulation of the capacitation-associated hyperpolarization in mouse sperm.. J Biol Chem 2006 Mar 3;281(9):5623-33.
        pubmed: 16407190doi: 10.1074/jbc.m508172200google scholar: lookup
      40. Seino S, Shibasaki T. PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis.. Physiol Rev 2005 Oct;85(4):1303-42.
        pubmed: 16183914doi: 10.1152/physrev.00001.2005google scholar: lookup
      41. Hernández-González EO, Treviño CL, Castellano LE, de la Vega-Beltrán JL, Ocampo AY, Wertheimer E, Visconti PE, Darszon A. Involvement of cystic fibrosis transmembrane conductance regulator in mouse sperm capacitation.. J Biol Chem 2007 Aug 17;282(33):24397-406.
        pubmed: 17588945doi: 10.1074/jbc.m701603200google scholar: lookup
      42. Arnoult C, Kazam IG, Visconti PE, Kopf GS, Villaz M, Florman HM. Control of the low voltage-activated calcium channel of mouse sperm by egg ZP3 and by membrane hyperpolarization during capacitation.. Proc Natl Acad Sci U S A 1999 Jun 8;96(12):6757-62.
        pmc: PMC21988pubmed: 10359785doi: 10.1073/pnas.96.12.6757google scholar: lookup
      43. Ster J, De Bock F, Guérineau NC, Janossy A, Barrère-Lemaire S, Bos JL, Bockaert J, Fagni L. Exchange protein activated by cAMP (Epac) mediates cAMP activation of p38 MAPK and modulation of Ca2+-dependent K+ channels in cerebellar neurons.. Proc Natl Acad Sci U S A 2007 Feb 13;104(7):2519-24.
        pmc: PMC1892910pubmed: 17284589doi: 10.1073/pnas.0611031104google scholar: lookup
      44. Kang G, Leech CA, Chepurny OG, Coetzee WA, Holz GG. Role of the cAMP sensor Epac as a determinant of KATP channel ATP sensitivity in human pancreatic beta-cells and rat INS-1 cells.. J Physiol 2008 Mar 1;586(5):1307-19.
        pmc: PMC2375670pubmed: 18202100doi: 10.1113/jphysiol.2007.143818google scholar: lookup
      45. Muñoz-Garay C, De la Vega-Beltrán JL, Delgado R, Labarca P, Felix R, Darszon A. Inwardly rectifying K(+) channels in spermatogenic cells: functional expression and implication in sperm capacitation.. Dev Biol 2001 Jun 1;234(1):261-74.
        pubmed: 11356034doi: 10.1006/dbio.2001.0196google scholar: lookup
      46. Florman HM, Jungnickel MK, Sutton KA. Regulating the acrosome reaction.. Int J Dev Biol 2008;52(5-6):503-10.
        pubmed: 18649263doi: 10.1387/ijdb.082696hfgoogle scholar: lookup
      47. Helms MN, Chen XJ, Ramosevac S, Eaton DC, Jain L. Dopamine regulation of amiloride-sensitive sodium channels in lung cells.. Am J Physiol Lung Cell Mol Physiol 2006 Apr;290(4):L710-L722.
        pubmed: 16284210doi: 10.1152/ajplung.00486.2004google scholar: lookup
      48. Aromataris EC, Roberts ML, Barritt GJ, Rychkov GY. Glucagon activates Ca2+ and Cl- channels in rat hepatocytes.. J Physiol 2006 Jun 15;573(Pt 3):611-25.
        pmc: PMC1779747pubmed: 16581855doi: 10.1113/jphysiol.2006.109819google scholar: lookup
      49. Lishko PV, Kirichok Y. The role of Hv1 and CatSper channels in sperm activation.. J Physiol 2010 Dec 1;588(Pt 23):4667-72.
        pmc: PMC3010136pubmed: 20679352doi: 10.1113/jphysiol.2010.194142google scholar: lookup

      Citations

      This article has been cited 17 times.
      1. Mendoza-Sánchez JE, Rodríguez-Tobón A, Arenas-Ríos E, Orta-Salazar GJ, León-Galván MA, Treviño Santa Cruz CL, Chávez JC. Sperm calcium flux and membrane potential hyperpolarization observed in the Mexican big-eared bat Corynorhinus mexicanus. J Exp Biol 2023 Jan 15;226(2).
        doi: 10.1242/jeb.244878pubmed: 36541225google scholar: lookup
      2. Maitan PP, Bromfield EG, Hoogendijk R, Leung MR, Zeev-Ben-Mordehai T, van de Lest CH, Jansen JWA, Leemans B, Guimarães JD, Stout TAE, Gadella BM, Henning H. Bicarbonate-Stimulated Membrane Reorganization in Stallion Spermatozoa. Front Cell Dev Biol 2021;9:772254.
        doi: 10.3389/fcell.2021.772254pubmed: 34869370google scholar: lookup
      3. Jin SK, Yang WX. Factors and pathways involved in capacitation: how are they regulated?. Oncotarget 2017 Jan 10;8(2):3600-3627.
        doi: 10.18632/oncotarget.12274pubmed: 27690295google scholar: lookup
      4. Huang Q, Luo L, Alamdar A, Zhang J, Liu L, Tian M, Eqani SA, Shen H. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity. Sci Rep 2016 Sep 2;6:32518.
        doi: 10.1038/srep32518pubmed: 27585557google scholar: lookup
      5. Goupil S, Maréchal L, El Hajj H, Tremblay MÈ, Richard FJ, Leclerc P. Identification and Localization of the Cyclic Nucleotide Phosphodiesterase 10A in Bovine Testis and Mature Spermatozoa. PLoS One 2016;11(8):e0161035.
        doi: 10.1371/journal.pone.0161035pubmed: 27548062google scholar: lookup
      6. Escoffier J, Navarrete F, Haddad D, Santi CM, Darszon A, Visconti PE. Flow cytometry analysis reveals that only a subpopulation of mouse sperm undergoes hyperpolarization during capacitation. Biol Reprod 2015 May;92(5):121.
        doi: 10.1095/biolreprod.114.127266pubmed: 25855261google scholar: lookup
      7. Buffone MG, Wertheimer EV, Visconti PE, Krapf D. Central role of soluble adenylyl cyclase and cAMP in sperm physiology. Biochim Biophys Acta 2014 Dec;1842(12 Pt B):2610-20.
        doi: 10.1016/j.bbadis.2014.07.013pubmed: 25066614google scholar: lookup
      8. Naz RK. The Effect of Curcumin on Intracellular pH (pHi), Membrane Hyperpolarization and Sperm Motility. J Reprod Infertil 2014 Apr;15(2):62-70.
        pubmed: 24918078
      9. López-González I, Torres-Rodríguez P, Sánchez-Carranza O, Solís-López A, Santi CM, Darszon A, Treviño CL. Membrane hyperpolarization during human sperm capacitation. Mol Hum Reprod 2014 Jul;20(7):619-29.
        doi: 10.1093/molehr/gau029pubmed: 24737063google scholar: lookup
      10. Vadnais ML, Aghajanian HK, Lin A, Gerton GL. Signaling in sperm: toward a molecular understanding of the acquisition of sperm motility in the mouse epididymis. Biol Reprod 2013 Nov;89(5):127.
        doi: 10.1095/biolreprod.113.110163pubmed: 24006282google scholar: lookup
      11. De La Vega-Beltran JL, Sánchez-Cárdenas C, Krapf D, Hernandez-González EO, Wertheimer E, Treviño CL, Visconti PE, Darszon A. Mouse sperm membrane potential hyperpolarization is necessary and sufficient to prepare sperm for the acrosome reaction. J Biol Chem 2012 Dec 28;287(53):44384-93.
        doi: 10.1074/jbc.M112.393488pubmed: 23095755google scholar: lookup
      12. Figueiras-Fierro D, Acevedo JJ, Martínez-López P, Escoffier J, Sepúlveda FV, Balderas E, Orta G, Visconti PE, Darszon A. Electrophysiological evidence for the presence of cystic fibrosis transmembrane conductance regulator (CFTR) in mouse sperm. J Cell Physiol 2013 Mar;228(3):590-601.
        doi: 10.1002/jcp.24166pubmed: 22833409google scholar: lookup
      13. Miro-Moran A, Jardin I, Ortega-Ferrusola C, Salido GM, Peña FJ, Tapia JA, Aparicio IM. Identification and function of exchange proteins activated directly by cyclic AMP (Epac) in mammalian spermatozoa. PLoS One 2012;7(5):e37713.
        doi: 10.1371/journal.pone.0037713pubmed: 22662198google scholar: lookup
      14. Escoffier J, Krapf D, Navarrete F, Darszon A, Visconti PE. Flow cytometry analysis reveals a decrease in intracellular sodium during sperm capacitation. J Cell Sci 2012 Jan 15;125(Pt 2):473-85.
        doi: 10.1242/jcs.093344pubmed: 22302997google scholar: lookup
      15. Yousuf S, Malik WA, Feng H, Liu T, Xie L, Miao X. Integrated analysis of microRNA and mRNA interactions regulating fecundity in the ovaries of two distinct sheep breeds. BMC Genomics 2025 Jul 31;26(1):707.
        doi: 10.1186/s12864-025-11408-0pubmed: 40745523google scholar: lookup
      16. Felix MR, Dobbie T, Woodward E, Linardi R, Okada C, Santos R, Hinrichs K. Equine in vitro fertilization with frozen-thawed semen is associated with shortened pre-incubation time and modified capacitation-related changes. Biol Reprod 2025 May 13;112(5):867-879.
        doi: 10.1093/biolre/ioaf043pubmed: 40057974google scholar: lookup
      17. Takei GL. Molecular mechanisms of mammalian sperm capacitation, and its regulation by sodium-dependent secondary active transporters. Reprod Med Biol 2024 Jan-Dec;23(1):e12614.
        doi: 10.1002/rmb2.12614pubmed: 39416520google scholar: lookup
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