2023
A CUG-initiated CATSPERθ functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking
Huang X, Miyata H, Wang H, Mori G, Iida-Norita R, Ikawa M, Percudani R, Chung J. A CUG-initiated CATSPERθ functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304409120. PMID: 37725640, PMCID: PMC10523455, DOI: 10.1073/pnas.2304409120.Peer-Reviewed Original ResearchConceptsChannel assemblySperm flagellaTransmembrane domain-containing proteinsSperm tail formationDomain-containing proteinsCatSper channel complexMale fertilityFlagellar traffickingMacromolecular complexesTail formationPhysiological roleSuccessful fertilizationCalcium signalingCatSper channelsFlagellaGenetic abrogationChannel complexNormal expressionDimer formationSpermatid cellsProteinCheckpointHyperactivated motilityAssemblyPotential role
2022
Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction
Griffin KN, Walters BW, Li H, Wang H, Biancon G, Tebaldi T, Kaya CB, Kanyo J, Lam TT, Cox AL, Halene S, Chung JJ, Lesch BJ. Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction. Genome Research 2022, 32: 1655-1668. PMID: 36109149, PMCID: PMC9528986, DOI: 10.1101/gr.276578.122.Peer-Reviewed Original ResearchMammalian male reproductionArgonaute 2Distinct nuclear functionsConditional knockoutMale reproductionProtein Argonaute 2Abnormal sperm head morphologyMeiotic chromatinAnimal developmentCytoplasmic roleNuclear functionsMale meiosisNuclear roleMRNA translationAgo2 proteinImportant genesNuclear compartmentMRNA transcriptsBiological relevanceSperm head morphologyHead morphologySpermatogenic cellsWidespread associationChromatinProteinSelenoprotein TXNRD3 supports male fertility via the redox regulation of spermatogenesis
Dou Q, Turanov AA, Mariotti M, Hwang JY, Wang H, Lee SG, Paulo JA, Yim SH, Gygi SP, Chung JJ, Gladyshev VN. Selenoprotein TXNRD3 supports male fertility via the redox regulation of spermatogenesis. Journal Of Biological Chemistry 2022, 298: 102183. PMID: 35753352, PMCID: PMC9352919, DOI: 10.1016/j.jbc.2022.102183.Peer-Reviewed Original ResearchConceptsThioredoxin/glutathione reductaseThiol redox controlSperm quality controlThiol redox statusGene duplicationThiol oxidoreductasesRedox regulationProteomic analysisRedox controlGross phenotypeThioredoxin reductaseSperm maturationMovement phenotypesSperm cellsRedox statusMale reproductionKnockout animalsMale fertilityGlutathione reductaseCritical roleReductasePhenotypeTXNRD3Knockout miceSpermatogenesis3D structure and in situ arrangements of CatSper channel in the sperm flagellum
Zhao Y, Wang H, Wiesehoefer C, Shah NB, Reetz E, Hwang JY, Huang X, Wang TE, Lishko PV, Davies KM, Wennemuth G, Nicastro D, Chung JJ. 3D structure and in situ arrangements of CatSper channel in the sperm flagellum. Nature Communications 2022, 13: 3439. PMID: 35715406, PMCID: PMC9205950, DOI: 10.1038/s41467-022-31050-8.Peer-Reviewed Original ResearchConceptsCatSper complexSperm flagellaCryo-electron tomographyHigher-order organizationMammalian spermIntracellular domainStructural basisExtracellular domainTetrameric channelChannel CatSperSuccessful fertilizationFlagellar movementCatSper channelsChannel poreSitu mapSitu arrangementHuman sperm flagellumPrimary Ca2CatSperDimer formationFlagellaCentral roleSpermAtomic modelSperm motilityRedox regulation by TXNRD3 during epididymal maturation underlies capacitation-associated mitochondrial activity and sperm motility in mice
Wang H, Dou Q, Jeong KJ, Choi J, Gladyshev VN, Chung JJ. Redox regulation by TXNRD3 during epididymal maturation underlies capacitation-associated mitochondrial activity and sperm motility in mice. Journal Of Biological Chemistry 2022, 298: 102077. PMID: 35643315, PMCID: PMC9218152, DOI: 10.1016/j.jbc.2022.102077.Peer-Reviewed Original ResearchConceptsRedox regulationRedox homeostasisMolecular mechanismsSperm maturationMitochondrial sheath formationCell imaging analysisThioredoxin glutathione reductaseSperm developmentMammalian spermatozoaEpididymal transitMitochondrial ultrastructureMitochondrial activityRedox statusMale fertilityCapacitationHomeostasisMaturationRegulationMotilityFamily membersFertilizationSperm morphologySperm motilityMitochondriaBioenergeticsC2cd6-encoded CatSperτ targets sperm calcium channel to Ca2+ signaling domains in the flagellar membrane
Hwang JY, Wang H, Lu Y, Ikawa M, Chung JJ. C2cd6-encoded CatSperτ targets sperm calcium channel to Ca2+ signaling domains in the flagellar membrane. Cell Reports 2022, 38: 110226. PMID: 34998468, PMCID: PMC8857959, DOI: 10.1016/j.celrep.2021.110226.Peer-Reviewed Original ResearchConceptsFlagellar membraneFlagellar membrane targetingC2 domain proteinsCatSper channelsCatSper channel complexMammalian sperm cellsSperm hyperactivated motilityMale fertilityMembrane targetingTrafficking machineryDomain proteinsLoss of functionHyperactivated motilitySpatiotemporal CaChannel assemblyMolecular mechanismsSperm cellsChannel complexFlagellaMotilityC2CD6MembraneCalcium channelsMachineryProtein
2021
Mitochondria–cytoskeleton interactions in mammalian sperm revealed by cryoelectron tomography
Wang H, Chung JJ. Mitochondria–cytoskeleton interactions in mammalian sperm revealed by cryoelectron tomography. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2118020118. PMID: 34819381, PMCID: PMC8640839, DOI: 10.1073/pnas.2118020118.Commentaries, Editorials and LettersPhysiologically detectable bisphenol A impairs human sperm functions by reducing protein-tyrosine phosphorylation
Li N, Kang H, Peng Z, Wang H, Weng S, Zeng X. Physiologically detectable bisphenol A impairs human sperm functions by reducing protein-tyrosine phosphorylation. Ecotoxicology And Environmental Safety 2021, 221: 112418. PMID: 34146982, DOI: 10.1016/j.ecoenv.2021.112418.Peer-Reviewed Original ResearchConceptsHuman sperm viabilityHuman sperm functionHuman spermExposure of BPASperm functionProgesterone-induced acrosome reactionProtein tyrosine phosphorylationProtein tyrosine phosphorylation levelsAcrosome reactionMale infertilityHealthy peopleMouse sperm motilitySperm viabilityCalcium signalingPhosphorylation levelsTyrosine phosphorylation levelsBisphenol ASperm motilityProgressive motilityHyperactivationMotilityDetectable concentrationRemarkable declineTyrosine phosphorylationPlastic monomersGenetic Defects in DNAH2 Underlie Male Infertility With Multiple Morphological Abnormalities of the Sperm Flagella in Humans and Mice
Hwang JY, Nawaz S, Choi J, Wang H, Hussain S, Nawaz M, Lopez-Giraldez F, Jeong K, Dong W, Oh JN, Bilguvar K, Mane S, Lee CK, Bystroff C, Lifton RP, Ahmad W, Chung JJ. Genetic Defects in DNAH2 Underlie Male Infertility With Multiple Morphological Abnormalities of the Sperm Flagella in Humans and Mice. Frontiers In Cell And Developmental Biology 2021, 9: 662903. PMID: 33968937, PMCID: PMC8103034, DOI: 10.3389/fcell.2021.662903.Peer-Reviewed Original ResearchMultiple morphological abnormalitiesMale infertility casesMorphological abnormalitiesWhole-exome sequencingIrregular flagellaInfertility casesSperm flagella formationMMAF phenotypeSevere formMale infertilityAsthenozoospermic patientsMutant miceNon-synonymous variantsAbnormalitiesRecessive variantsCellular mechanismsGenetic factorsMMAFGenetic defectsPatientsMiceHeavy chain domainSperm morphologyAsthenozoospermiaSperm motility
2020
Sperm ion channels and transporters in male fertility and infertility
Wang H, McGoldrick LL, Chung JJ. Sperm ion channels and transporters in male fertility and infertility. Nature Reviews Urology 2020, 18: 46-66. PMID: 33214707, PMCID: PMC7852504, DOI: 10.1038/s41585-020-00390-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSperm ion channelsIon channelsSperm cellsMammalian sperm cellsIon signalingDynamic regulationDefective sperm functionFemale reproductive tractChannel CatSperHuman geneticsMembrane receptorsMale fertilityHealth careAttractive targetDirect electrophysiological recordingsOverall health careHuman infertilityReproductive health careSperm functionPrincipal Ca2Development of contraceptivesSperm activityGene variantsReproductive tractGenetic abnormalities
2019
A novel copy number variation in CATSPER2 causes idiopathic male infertility with normal semen parameters
Luo T, Chen H, Zou Q, Wang T, Cheng Y, Wang H, Wang F, Jin Z, Chen Y, Weng S, Zeng X. A novel copy number variation in CATSPER2 causes idiopathic male infertility with normal semen parameters. Human Reproduction 2019, 34: 414-423. PMID: 30629171, DOI: 10.1093/humrep/dey377.Peer-Reviewed Original ResearchConceptsIdiopathic male infertilityNormal semen parametersWhole-cell patch-clamp techniqueMale infertilityPatch-clamp techniqueSemen parametersCatSper currentsIdiopathic infertilitySTUDY FUNDING/COMPETINGGenetic abnormalitiesCatSper genesChild Health HospitalReproductive medical centerNovel copy number variationsPARTICIPANTS/MATERIALSROLE OF CHANCEHuman male infertilityHealthy male donorsCopy number variationsHuman CatSperPrinciple Ca2Progesterone responseCase reportProvincial MaternalHealth Hospital
2017
Exposure to Cadmium Impairs Sperm Functions by Reducing CatSper in Mice
Wang H, Chang M, Peng T, Yang Y, Li N, Luo T, Cheng Y, Zhou M, Zeng X, Zheng L. Exposure to Cadmium Impairs Sperm Functions by Reducing CatSper in Mice. Cellular Physiology And Biochemistry 2017, 42: 44-54. PMID: 28554186, DOI: 10.1159/000477113.Peer-Reviewed Original ResearchConceptsAdult male C57BL/6 miceMale C57BL/6 miceImpair sperm functionAcute cadmium exposureSperm functionSperm-specific Ca2C57BL/6 miceReproductive toxicityCadmium exposureWestern blottingDifferent dosesSperm dysfunctionExpression levelsEnvironmental heavy metalsToxic effectsMiceEndocrine disruptorsCatSperSperm motilityMouse spermatozoaSpecific roleToxicityExposureMotilityDysfunction
2016
Diethylstilbestrol activates CatSper and disturbs progesterone actions in human spermatozoa
Zou Q, Peng Z, Zhao Q, Chen H, Cheng Y, Liu Q, He Y, Weng S, Wang H, Wang T, Zheng L, Luo T. Diethylstilbestrol activates CatSper and disturbs progesterone actions in human spermatozoa. Human Reproduction 2016, 32: 290-298. PMID: 28031325, DOI: 10.1093/humrep/dew332.Peer-Reviewed Original ResearchConceptsNon-genomic mannerProgesterone actionHuman sperm functionEndocrine-disrupting chemicalsSperm intracellular calcium concentrationsWhole-cell patch-clamp techniqueSperm functionHuman spermatozoaPARTICIPANTS/MATERIALSHuman sperm penetrationIndicator Fluo-4 AMIntracellular calcium concentrationROLE OF CHANCEAcrosome reactionEffects of diethylstilbestrolPatch-clamp techniqueFluo-4 AMFemale reproductive tract fluidsMale reproductive systemTyrosine phosphorylationReproductive tract fluidsDES exposurePostnatal exposureEstrogenic endocrine disruptorsAbility of spermBisphenol A Impairs Mature Sperm Functions by a CatSper-Relevant Mechanism
Wang H, Liu M, Li N, Luo T, Zheng L, Zeng X. Bisphenol A Impairs Mature Sperm Functions by a CatSper-Relevant Mechanism. Toxicological Sciences 2016, 152: 145-154. PMID: 27125968, DOI: 10.1093/toxsci/kfw070.Peer-Reviewed Original ResearchConceptsToxicity of BPANormal mouse spermSperm functionMature sperm functionVivo administrationEndocrine-disrupting chemicalsWestern blotDifferent dosesSignificant decreaseSperm total motilitySignificant reductionBisphenol AMiceSperm motilityMouse spermMouse spermatozoaMotilityCatSperTotal motilityToxicityMatrine compromises mouse sperm functions by a [Ca2+]i-related mechanism
Luo T, Zou Q, He Y, Wang H, Wang T, Liu M, Chen Y, Wang B. Matrine compromises mouse sperm functions by a [Ca2+]i-related mechanism. Reproductive Toxicology 2016, 60: 69-75. PMID: 26867864, DOI: 10.1016/j.reprotox.2016.02.003.Peer-Reviewed Original ResearchConceptsMouse sperm functionSperm functionDaily dosesIntraperitoneal injectionMale miceSperm countTestis weightReproductive toxicityMiceChinese medicineCatSper channelsMatrineProgressive motilityAcrosome reactionKey regulatorMouse spermTotal motilitySperm viabilityGene expressionTestis sizeMotilitySpermDoses
2015
Matrine Inhibits Mouse Sperm Function by Reducing Sperm [Ca2+]i and Phospho-ERK1/2
Luo T, Zou Q, He Y, Wang H, Li N, Zeng X. Matrine Inhibits Mouse Sperm Function by Reducing Sperm [Ca2+]i and Phospho-ERK1/2. Cellular Physiology And Biochemistry 2015, 35: 374-385. PMID: 25591778, DOI: 10.1159/000369703.Peer-Reviewed Original ResearchMeSH KeywordsAcrosome ReactionAlkaloidsAniline CompoundsAnimalsCalcimycinCalciumFemaleFertilization in VitroMaleMatrinesMiceMice, Inbred C57BLMicroscopy, FluorescenceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Patch-Clamp TechniquesPhosphorylationPotassiumQuinolizinesSperm MotilitySpermatozoaXanthenesConceptsMouse sperm functionIntracellular calcium concentrationSperm functionCauda epididymal spermMouse spermPhosphorylation of ERK1/2Acrosome reaction rateEpididymal spermMouse cauda epididymal spermFertilization abilityPharmacological effectsPotassium currentP-ERK1/2Phospho-ERK1/2Calcium concentrationChinese medicineKinase 1/2Male reproductionSignificant reductionMatrineMature mouse spermProgressive motilityAcrosome reactionMotilityTotal motility
2013
Sperm-specific ion channels: targets holding the most potential for male contraceptives in development
Zheng L, Wang H, Li B, Zeng X. Sperm-specific ion channels: targets holding the most potential for male contraceptives in development. Contraception 2013, 88: 485-491. PMID: 23845210, DOI: 10.1016/j.contraception.2013.06.002.Peer-Reviewed Original ResearchMeSH KeywordsAnoctamin-1Calcium ChannelsChloride Channel AgonistsChloride ChannelsContraceptive Agents, MaleDrugs, InvestigationalHumansIon ChannelsLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsLarge-Conductance Calcium-Activated Potassium ChannelsMaleMembrane ProteinsNeoplasm ProteinsOrgan SpecificityPotassium Channels, Voltage-GatedProtein SubunitsSignal TransductionSpermatozoa