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卵巢基质中局部NGF的表达通过mTOR信号通路诱导原始卵泡激活.docx

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卵巢基质中局部NGF的表达通过mTOR信号通路诱导原始卵泡激活 Title:mTORSignalingPathwayInducesActivationofPrimordialFolliclesthroughLocalNGFExpressioninOvarianStroma Abstract: Ovarianfolliculogenesisisacomplexprocessregulatedbyvarioussignalingpathways,suchasthemTOR(mammaliantargetofrapamycin)pathwayandtheneurotrophinnervegrowthfactor(NGF).Inthisstudy,weinvestigatedtheroleoflocalNGFexpressionanditsinteractionwiththemTORsignalingpathwayintheactivationofprimordialfolliclesintheovarianstroma.OurfindingssuggestthatincreasedmTORactivityinducestheexpressionofNGFintheovarianstroma,leadingtotheactivationofprimordialfolliclesandsubsequentfollicledevelopment. Introduction: Theovarianstromaplaysacrucialroleinfollicledevelopmentandfunction.Primordialfollicles,consistingofdormantoocytessurroundedbyasinglelayerofflattenedgranulosacells,areconsideredtherestingstageoffolliculardevelopment.Activationofprimordialfolliclesresultsintherecruitmentofacohortoffolliclesfordevelopmentandeventualovulation.Themechanismsunderlyingtheactivationofprimordialfolliclesarenotfullyunderstood.However,emergingevidencesuggeststhatthemTORsignalingpathwayandlocalNGFexpressionintheovarianstromamayplaypivotalrolesinthisprocess. mTORSignalingPathwayandFolliculogenesis: ThemTORsignalingpathwayisahighlyconservedpathwaythatcontrolscellgrowth,proliferation,andsurvival.Intheovaries,themTORpathwayhasbeenimplicatedinvariousstagesoffolliculogenesis,includingprimordialfollicleactivation.ActivationofmTORleadstoincreasedproteinsynthesis,cellgrowth,andproliferation. InitialstudieshaveshownthatactivationofthemTORpathwayintheovarianstromaisassociatedwiththeactivationofprimordialfollicles.InhibitingmTORactivityusingrapamycin,aspecificinhibitorofmTORcomplex1(mTORC1),hasbeenfoundtosuppressprimordialfollicleactivationanddisruptfollicledevelopment.ThesefindingsindicatetheimportantroleofthemTORpathwayinregulatingfollicleactivation. NGFExpressionintheOvarianStroma: NGF,amemberoftheneurotrophinfamily,isknowntopromoteneuronalsurvival,proliferation,anddifferent