Molecular Mechanism for Human Sperm Chemotaxis Mediated by Progesterone 英文参考文献.docVIP

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Molecular Mechanism for Human Sperm Chemotaxis Mediated by Progesterone 英文参考文献.doc

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MolecularMechanismforHumanSpermChemotaxis MediatedbyProgesterone MariaE.Teves1,HectorA.Guidobaldi1,DiegoR.Un?ates1,RaulSanchez2,WernerMiska3,StephenJ. Publicover4,Adue′nA.MoralesGarcia4,LauraC.Giojalas1* 1CentrodeBiolog?′aCelularyMolecular,UniversidadNacionaldeCo′rdoba,Co′rdoba,Argentina,2CentrodeBiotecnolog?′adelaReproduccio′n,DepartamentodeCiencias Precl?′nicas, Universidad de La Frontera, Temuco, Chile, 3Centre for Dermatology and Andrology, Justus Liebig University, Giessen, Germany, 4School of Biosciences, UniversityofBirmingham,Birmingham,UnitedKingdom Abstract Sperm chemotaxis is a chemical guiding mechanism that may orient spermatozoa to the egg surface. A picomolar concentrationgradientofProgesterone(P),themainsteroidalcomponentsecretedbythecumuluscellsthatsurroundthe egg,attractshumanspermatozoa.InordertoelucidatethemolecularmechanismofspermchemotaxismediatedbyP,we combine the application of different strategies: pharmacological inhibition of signaling molecules, measurements of the concentrationsofsecondmessengersandactivationofthechemotacticsignaling.Ourdataimplicateanumberofclassic signaltransductionpathwaysintheresponseandprovideamodelforthesequenceofevents,wherethetmAC-cAMP-PKA pathway is activated first, followed by protein tyrosine phosphorylation (equatorial band and flagellum) and calcium mobilization(throughIP3RandSOCchannels),whereasthesGC-cGMP-PKGcascade,isactivatedlater.Theseeventsleadto sperm orientation towards the source of the chemoattractant. The finding proposes a molecular mechanism which contributes to the understanding of the signal transduction pathway that takes place in a physiological process as chemotaxis. Citation: Teves ME, Guidobaldi HA, Un?ates DR, Sanchez R, Miska W, et al. (2009) Molecular Mechanism for Human Sperm Chemotaxis Mediated by Progesterone.PLoSONE4(12):e8211.doi:10.1371/journal.pone.0008211 Editor:ImmoA.Hansen,NewMexicoStateUniversity,UnitedStatesofAmerica ReceivedAugust7,2009;AcceptedOctober31,2009;PublishedDe